MODULE

11: ENDOCRINE SYSTEM

Molecular Biology of Hormones

03/30/2020
BIOCHEMISTRY & PHYSIOLOGY

TABLE OF CONTENTS • Autocrines
o Secreted by cells into the extracellular fluid
I. BASIC CONCEPTS OF ENDOCRINOLOGY .................................................................... 1 o Affect the function of the same cells that produced them
A. CHEMICAL MESSENGERS ................................................................................... 1 • Cytokines
B. OVERVIEW OF ENDOCRINE HORMONES ............................................................ 1 o Peptides secreted by cells into the extracellular fluid
II. GENERAL CLASSES OF HORMONES .......................................................................... 2
A. POLYPEPTIDE AND PROTEIN HORMONES .......................................................... 2 o Can function as autocrine, paracrine, or endocrine hormones
B. STEROID HORMONES ......................................................................................... 2 § e.g. Interleukins and other lymphokines secreted by helper cells
C. AMINE HORMONES ............................................................................................ 3 and act on other cells of the immune system
III. SECRETION OF HORMONES ..................................................................................... 3 o Adipokines
A. FEEDBACK CONTROL OF HORMONES ................................................................ 3 § Cytokine hormones (e.g. Leptin) produced by adipocytes
IV. TRANSPORT OF HORMONES ................................................................................... 3
A. WATER-SOLUBLE HORMONES ........................................................................... 3
B. LIPID-SOLUBLE HORMONES ............................................................................... 3 B. OVERVIEW OF ENDOCRINE HORMONES
V. HORMONE CLEARANCE ............................................................................................ 4
A. OVERVIEW .......................................................................................................... 4
B. CLEARANCE FROM PLASMA ............................................................................... 4
VI. MECHANISM OF ACTION OF HORMONES ............................................................... 4
A. RECEPTOR BINDING ........................................................................................... 4
B. INTRACELLULAR SIGNALING ............................................................................... 4
C. SECOND MESSENGER SYSTEMS ......................................................................... 6
D. DIRECT ACTION ON THE CELLULAR GENETIC MACHINERY ................................ 7
VII. MEASUREMENT OF HORMONE CONCENTRATIONS IN THE BLOOD ...................... 7
A. RADIOIMMUNOASSAY ....................................................................................... 7
B. ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) .......................................... 7
QUICK REVIEW ............................................................................................................. 8
SUMMARY OF TERMS ............................................................................................ 8
SUMMARY OF PROCESSES ..................................................................................... 8
EQUATIONS ............................................................................................................ 9
REVIEW QUESTIONS ............................................................................................... 9
REFERENCES ............................................................................................................... 10
REQUIRED ............................................................................................................. 10
FREEDOM SPACE ........................................................................................................ 10
APPENDIX ................................................................................................................... 11


NOTE: According to Doc Canto, the main reference for this topic is Chapter
th
75 of Guyton and Hall Textbook of Medical Physiology, 13 edition. The
trans group, however, decided to include some pertinent information from
Batch 2023’s trans that were not in the book to further our understanding
and knowledge on the topic. Figure 1. Anatomical loci of the principal endocrine glands and tissues of the
body (Placenta, an additional source of sex hormones, is not shown)

I. BASIC CONCEPTS OF ENDOCRINOLOGY • Endocrine hormones
o Transported by the circulatory system to cells throughout the body,
A. CHEMICAL MESSENGERS including the nervous system, where they bind with receptors and
• Coordinate the multiple activities of cells, tissues, and organs of the body initiate many cell reactions
• Interact with one another to maintain homeostasis o Some affect many different types of cells
• Examples: § Growth hormone
o Adrenal medulla and pituitary gland secrete their hormones primarily Þ Secreted by the anterior pituitary gland
in response to neural stimuli Þ Leads to growth in most parts of the body
o Axons of hypothalamic neuroendocrine cells that terminate in the § Thyroxine
posterior pituitary gland and median eminence secrete neurohormones Þ Secreted by the thyroid gland
(i.e., antidiuretic hormone, oxytocin, and hypophysiotropic hormones) Þ Increases the rate of many chemical reactions in almost all the
that control anterior pituitary secretions body’s cells
o Some affect specific target tissues due to the abundance of receptors
Types of Chemical Messengers for certain hormones in these tissues
• Neurotransmitters § Adrenocorticotropic hormone
o Released by axon terminals of neurons into synaptic junctions Þ Secreted by the anterior pituitary gland
o Act locally to control neuronal functions Þ Stimulates the adrenal cortex to release adrenocortical
• Endocrine hormones hormones
o Released by glands or specialized cells directly into the bloodstream § Ovarian hormones
o Influence the function of target cells at a distant location in the body Þ Affect female sex organs and influence the development of
• Neuroendocrine hormones secondary sexual characteristics in females
o Secreted by neurons into the bloodstream
o Influence the function of target cells at a distant location in the body Table 1. Endocrine Glands, Hormones, Structures and Functions [Refer to
• Paracrines Appendix A]
o Secreted by cells into the extracellular fluid
o Affect neighboring target cells of a different type

Transcribed by TG 11: Ballelos, Cortez, Gamo, Lacerna, Lim, Monge, Pagayatan, Sanchez
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Checked by TG 23: Catacutan, Daco, Go, Luna, Mamaril, Mariano, Rita, Sing 1 of 11



• The multiple hormone systems play a key role in regulating almost all body 4) Enzymes in the vesicles cleave the prohormones to create biologically
functions such as: active hormones and inactive fragments
o Metabolism 5) Vesicles are either stored within the cytoplasm or bound to the cell
§ Without insulin (from the pancreas), the body’s cells could use little membrane until secretion is needed
of the carbohydrates in food for energy
§ Without thyroxine (from the thyroid gland) and triiodothyronine, B. STEROID HORMONES
almost all the chemical reactions of the body would become
• Secreted by the adrenal cortex, ovaries, testes, and placenta
sluggish, causing the person to become sluggish as well
• Consist of 3 cyclohexyl rings and 1 cyclopentyl ring, similar to cholesterol
o Growth and development
• Usually synthesized from cholesterol and are not stored
§ Without growth hormone, a person would be a dwarf
o When needed, large stores of cholesterol esters in the cytoplasm
o Water and electrolyte balance
vacuoles are used to synthesize steroids
o Reproduction
o Despite having similar chemical formulas, slight differences in
§ Without sex hormones, sexual development and sexual functions
molecular structures give rise to different functions
would be absent
o Much of the cholesterol in steroid-producing cells comes from plasma,
o Behavior
but some are still produced through de novo synthesis

• Lipid-soluble
II. GENERAL CLASSES OF HORMONES o Capable of diffusing across the cell membrane, into the interstitial fluid,
• While there are hormones that are primarily proteins and lipids (steroids), and then into the blood after synthesis
note that there are no known polysaccharide or nucleic acid hormones

A. POLYPEPTIDE AND PROTEIN HORMONES
• Secreted by the anterior and posterior pituitary gland, pancreas (insulin
and glucagon), parathyroid gland (parathyroid hormone), etc.
• Most of the hormones in the body are of this type
• Water-soluble
o Facilitates their easy entry into the bloodstream for faster release to
target organs
• Sizes range from 3 (thyrotropin-releasing hormone) to almost 200 (growth
hormone and prolactin) amino acids Figure 3. Steroid Hormone Basic Structure
o To differentiate peptides from protein hormones, their sizes are
considered Synthesis
§ Peptides: < 100 amino acids
§ Proteins: ≥ 100 amino acids NOTE: This section was lifted from Batch 2023’s trans, 12.02: Molecular
• Secreted via exocytosis Biology of Hormones & Action.
o Vesicles fuse with the cell membrane and contents are extruded out
into the interstitial fluid
o Stimuli for the release of hormones:
§ Increased cytosolic calcium concentration due to the depolarization
of the plasma membrane
1
§ Increased cyclic adenosine monophosphate (cAMP ) and
subsequent activation of protein kinases
Þ Caused by stimulation of an endocrine cell surface receptor
! Stored in secretory vesicles until needed

Synthesis

Figure 4. Synthesis of Steroid Hormones

1) Hormonal stimulation of steroidogenic cells

2
2) Hydrolysis of Cholesteryl Esters (CE ) stored in lipid droplets to liberate free
Cholesterol
o Enzyme: CE Hydrolase
3) Sterol Carrier Protein-2 delivers Cholesterol from the cytoplasm to the
outer mitochondrial membrane
3
4) De novo synthesis of Steroidogenic Acute Regulatory Protein (StAR )
o StAR is made only when needed
Figure 2. Synthesis and Secretion of Peptide Hormones 5) StAR facilitates the translocation of Cholesterol from the outer to the inner
mitochondrial membrane
1) Synthesized first in the rough endoplasmic reticulum as larger proteins o It is eventually degraded in the mitochondrial matrix
called preprohormones which are not biologically active 6) Cholesterol is converted to Pregnenolone by side chain cleavage
2) Preprohormones are cleaved to form prohormones o Enzyme: P450SCC/Cholesterol Desmolase/CYP11A1
3) From the rough endoplasmic reticulum, prohormones are transferred to o Rate-limiting step of steroidogenesis
the Golgi apparatus for packaging into secretory vesicles o Pregnenolone is the first steroid synthesized
7) Pregnenolone is further metabolized to form various steroids in the body



1 3
cAMP: Cyclic adenosine monophosphate StAR: Steroidogenic acute regulatory protein
2
CE: Cholesteryl Esters

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C. AMINE HORMONES III. SECRETION OF HORMONES
• Derivatives of Tyrosine • Varying onset and duration tailored to the specific function of the
• Formed by the actions of enzymes in the cytoplasmic compartments of the hormone
glandular cells o e.g. Epinephrine and norepinephrine only take seconds to minutes to
take full effect, while thyroxine and growth hormone may take months
Thyroid Hormones • Concentration of hormones in circulation is incredibly small
o As little as one picogram to a few micrograms per milliliter of blood
• Thyroxine (T4) and Triiodothyronine (T3)
• Secretion rate is also extremely low
• Synthesized and stored in the thyroid gland
o Measured in micrograms or milligrams per day
! Taken up into preformed vesicles and stored until secreted


Synthesis and Secretion A. FEEDBACK CONTROL OF HORMONES
1) Incorporated into the macromolecules of the protein thyroglobulin, which Negative Feedback
are stored in large follicles within the thyroid gland • Prevents overactivity of hormone systems
2) When amines are split from thyroglobulin, the free hormones are released o The hormone itself, its products, or conditions resulting from hormonal
into the blood stream action tend to suppress its further release
3) Hormones bind to plasma proteins, especially thyroxine-binding globulin • Ensures proper level of hormone activity in the target tissue
4) They are then slowly released into the target tissues • Factors that may determine negative feedback:
o Secretory rate of hormone
Catecholamines o Degree of activity of target tissue
• Epinephrine and Norepinephrine § Only when target tissue activity is at an appropriate level will
o Four times more epinephrine is secreted compared to norepinephrine feedback signals slow further secretion of the endocrine gland
• Synthesized by the adrenal medulla • Feedback regulation can occur at all levels including:
• Stored in secretory granules and then released by exocytosis, similar to o Steps involved in hormone synthesis
protein hormones § Gene transcription
• Once released in circulation, they can exist in their free form or bound to § Translation
other substances o Steps involved in processing or release of stored hormones

Synthesis Positive Feedback
• Occurs when the action of a hormone causes additional secretion of the
5
hormone, such as in the case of the Luteinizing Hormone (LH )
NOTE: This section was also lifted from Batch 2023’s trans, 12.02: Molecular

Biology of Hormones & Action, but since the listed steps were vague and
incomplete, additional information were taken from Greenspan’s Basic and EXAMPLE: LUTEINIZING HORMONE
th
Clinical Endocrinology, 10 edition. • Recall: The LH Surge in the menstrual cycle is a result of the stimulatory
effect of Estrogen on the anterior pituitary
• LH then stimulates further secretion of Estrogen, which causes more
secretion of LH
• When LH reaches a threshold concentration, negative feedback occurs

th
SOURCE: Guyton and Hall Textbook of Medical Physiology 13 Edition, (p. 929)


Cyclical Variations in Hormone Release
• Refers to the periodic variation in hormone release influenced by:
o Seasonal changes
o Stages of development
o Aging
o Diurnal cycle
o Sleep
• Superimposed on the negative and positive feedback mechanisms
• Usually due to changes in activity of neural pathways involved in control of
hormone release
• e.g. Growth Hormone
o Secretion is increased during early period of sleep, but is reduced in
later stages of sleep

Figure 5. Synthesis of Norepinephrine
IV. TRANSPORT OF HORMONES
1) Conversion of Tyrosine to L-Dopa
o Enzyme: Tyrosine Hydroxylase A. WATER-SOLUBLE HORMONES
o Rate-limiting step of catecholamine synthesis • Include peptide hormones and catecholamines
2) Conversion of L-Dopa to Dopamine • Dissolved in plasma
o Enzyme: DOPA Decarboxylase • Diffuse out of the capillaries, enter theinterstitial fluid, and eventually
3) Dopamine gets taken up into secretory vesicles reach the target cells
4
o Transporter: Vesicular Monoamine Transporter (VMAT )
4) Conversion of Dopamine to Norepinephrine B. LIPID-SOLUBLE HORMONES
o Enzyme: Dopamine b-Hydroxylase • Steroid hormones and thyroid hormones
5) Norepinephrine may either:
2+ • Usually bound to plasma proteins while circulating in the blood
o Be exocytosed from the cell due to Ca influx
o Less than 10% exist in free form
o Diffuse out of the granules back into the cytoplasm
• Bound hormones can’t easily diffuse across capillaries & reach target cells
§ Converted to Epinephrine
o Biologically inactive until they are unconjugated
Þ Enzyme: Phenylethanolamine-N-Methyltransferase
o Largely serve as reservoirs to replenish concentration of free hormones
6) Epinephrine is taken up by vesicles to be released
o Binding of plasma proteins to hormones greatly slows down clearance

of these hormones



4 5
VMAT: Vesicular Monoamine Transporter LH: Luteinizing Hormone

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V. HORMONE CLEARANCE Table 2. Location of Receptor and corresponding type of hormone or ligand
LOCATION OF RECEPTOR HORMONES
A. OVERVIEW Protein, peptide, and
• Factors affecting hormone concentration in the blood: Cell Membrane
catecholamine hormones
o Rate of hormone secretion Cytoplasm Different steroid hormones
o Metabolic Clearance Rate Nucleus Thyroid hormones
§ Rate of removal of the hormone from the blood
§ Expressed in number of milliliters of plasma cleared of the hormone
per minute (mL/min)
Receptor Regulation
§ To calculate, measure the following: • Number of receptors in a target cell does not remain constant due to:
Þ Rate of disappearance of the hormone from plasma o Inactivation or destruction of receptors during the course of their
Þ Plasma concentration of the hormone function
o Reactivation of receptors or manufacturing of new ones by cells
𝑟𝑎𝑡𝑒 𝑜𝑓 𝑑𝑖𝑠𝑎𝑝𝑝𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑜𝑓 ℎ𝑜𝑟𝑚𝑜𝑛𝑒 𝑓𝑟𝑜𝑚 𝑝𝑙𝑎𝑚𝑎
𝑀𝑒𝑡𝑎𝑏𝑜𝑙𝑖𝑐 𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑟𝑎𝑡𝑒 =
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑖𝑜𝑛 𝑜𝑓 ℎ𝑜𝑟𝑚𝑜𝑛𝑒 Downregulation
• Decreases the target tissue’s responsiveness to the hormone
Equation 1. Metabolic Clearance Rate • Involves a decrease in the number of active receptors due to:
o Increased hormone concentration
NCTK: MEASUREMENT OF THE METABOLIC CLEARANCE RATE o Increased binding with target cell receptors
1) Tag a purified solution of the hormone with a radioactive substance • At the cellular level, receptor downregulation can occur as a result of the
2) Infuse the radioactive hormone into the bloodstream at a constant rate following:
until it reaches a steady concentration o Inactivation of receptor molecules
3) The rate of disappearance of the radioactive hormone is the rate at o Inactivation of intracellular protein signaling molecules
which it is infused o Temporary sequestration of the receptor to the inside of the cell
4) The plasma concentration of the radioactive hormone is measured using § Far from the site of action of hormones that interact with cell
a standard radioactive counting procedure membrane receptors
5) The metabolic clearance rate is calculated with the given formula o Destruction of the receptors by lysosomes after they’re internalized
o Decreased production of the receptors
th
SOURCE: Guyton and Hall Textbook of Medical Physiology 13 ed., (p. 930)
Upregulation

• Increases the target tissue’s sensitivity to the stimulating effects of the
B. CLEARANCE FROM PLASMA hormones
• Hormones are cleared by: • Involves an increase in the number of receptors
o Metabolic destruction by tissues • Stimulating hormones induce any of the following:
o Binding with tissues o Increased receptor formation
o Hepatic excretion (bile) o Increased formation of intracellular signaling molecules by the target
o Renal excretion (urine) cell
• In some cases, decreased metabolic clearance may cause an excessively o Greater availability of the receptor for interaction with the hormone
high concentration of certain hormones
o e.g. Liver disease
B. INTRACELLULAR SIGNALING
§ The liver conjugates several steroid hormones for clearance into bile
§ When a person has a liver disease, these hormones are not • Hormones exert their effects by first forming a hormone-receptor complex
appropriately cleared and thus become present in the system high o This complex alters the function of the receptor
concentrations o Activated receptor initiates the hormonal effects
• Hormones may be degraded at their target cells
o Through endocytosis of the hormone-receptor complex Ion Channel-Linked Receptors
o The hormone is then metabolized in the cell • Associated with neurotransmitters
o Receptors are recycled back to the cell membrane o e.g. Acetylcholine and Norepinephrine
• Water-soluble hormones, such as peptide hormones and catecholamines, • Only a few hormones exert their actions through the activation of ion
circulate freely in the blood for only a short time channel receptors
o Usually degraded by enzymes in blood and tissues and then rapidly o Most of these hormones indirectly open and close ion channels by
excreted by the kidneys and liver coupling with G protein-linked and enzyme-linked receptors
o e.g. Angiotensin II
§ Half-life of Angiotensin II circulating in the blood is less than a minute Activation of Ion Channel-Linked Receptors
• Plasma-protein bound hormones, such as steroid and thyroid hormones, 1) Neurotransmitters bind to postsynaptic receptors
are cleared at slower rates 2) Binding causes a conformational change in the receptor, which usually
o Remain in circulation for several hours or days opens or closes a channel for one or more ions
! Half-life of adrenal steroids: 20 to 100 minutes o Example of ions that pass through these channels:
! Half-life of protein-bound thyroid hormones: 1 to 6 days § Sodium
§ Potassium
VI. MECHANISM OF ACTION OF HORMONES § Calcium
A. RECEPTOR BINDING 3) Altered movement of the ions through the channels causes subsequent
effects on the postsynaptic cells
Receptor Activation
• Receptors are highly specific for a single hormone G Protein-Linked Hormone Receptors
o Determines the type of hormone that will act on a particular tissue 6
• G-protein coupled receptors (GPCR ) are composed of seven
o Cells that lack receptors for the hormones don’t respond to them
transmembrane loops
• Each cell has around 2000-100,000 receptors
o The cytoplasmic part of the receptor (i.e., tail) is coupled to a
• Hormones must first bind to specific receptors on the target cell 7
heterotrimeric Guanosine Triphosphate (GTP )-binding protein (G
o Formation of a Hormone-Receptor Complex
protein)
• After binding, a cascade of intracellular actions is initiated § Comprised of 𝛂, 𝛃, and 𝛄 subunits
o Each stage becomes more powerfully activated § In its inactive state, the α, β, and γ subunits form a complex, with a
§ Amplifies the signal even when small concentrations of the hormone GDP molecule bound to the α subunit
are present and allows it to exert huge effects



6 7
GPCR: G Protein-Coupled Receptors GTP: Guanosine Triphosphate

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• Activated GPCRs indirectly regulate the activity of their target proteins by Leptin Receptors
coupling with G proteins
• G protein activation following receptor binding induces intracellular signals
that may:
o Open or close cell membrane channels
o Change the activity of an enzyme in the cytoplasm of the cell
o Activate gene transcription
8
• Some hormones may be coupled to inhibitory G proteins (Gi ) or
9
stimulatory G proteins (Gs )
o A hormone can either increase or decrease the activity of intracellular
enzymes depending on the coupling of G proteins

Activation of G Protein-Linked Receptors

Figure 7. Enzyme-Linked Leptin Receptor Mechanism

• Leptin
o Hormone secreted by adipocytes
o Important in the regulation of appetite and energy balance
• Leptin Receptor
o Dimer
o Member of the cytokine receptor family
o Do not have enzymatic activity but can signal through associated
enzymes
10
• JAK2
Figure 6. G Protein-Linked Receptor Mechanism o Tyrosine kinase of the Janus Kinase family
1) Binding of a hormone to the extracellular part of the receptor o One of the pathways through which leptin receptor signaling occurs
2) The receptor undergoes a conformational change o Mechanism:
3) Activation of the GDP-bound G proteins § Leptin binding causes a receptor conformational change
o The G protein associates with the cytoplasmic part of the receptor § Associated intracellular JAK2 molecules are phosphorylated and
o GDP bound to the α subunit is exchanged for GTP activated
§ The G protein is now in its active state § Activated JAK2 molecules phosphorylate other tyrosine residues
o α subunit dissociates with the trimeric complex and binds with another within the leptin receptor-JAK2 complex
intracellular signaling protein § Intracellular signal transduction occurs:
4) Intracellular signal proteins alter the activity of ion channels or other Þ Phosphorylation of signal transducer and activator of
11
intracellular enzymes transcription (STAT ) proteins
5) Termination of signaling results from: ! Cascade of phosphorylation influences nuclear activity and STAT
o Removal of the hormone proteins activate transcription of leptin target genes to initiate
o Consequent auto-inactivation of the α subunit by converting GTP to protein synthesis
GDP Þ Protein synthesis
§ The α subunit combines with β and γ subunits to reform the inactive § JAK2 phosphorylation also activates other enzyme systems (E.g.
12 13
membrane-bound trimeric G protein MAPK and PI3K ) that mediate physiological effects of leptin

Enzyme-Linked Hormone Receptors Adenylyl Cyclase
• Activated receptors that function directly as enzymes or are closely • Hormone binds to special transmembrane receptor
associated with enzymes • Cytoplasmic end of the receptor becomes the activated adenylyl cyclase
• Transmembrane proteins that pass through the membrane only once • Catalyzes the formation of cAMP
• Hormone-binding site is on the extracellular domain of the cell o Considered as a second messenger because it is not the hormone itself
membrane, and the enzyme-binding (catalytic) site is on the intracellular that directly causes the intracellular changes
14
domain • cGMP serves as the secondary messenger for some peptide hormones
o When a ligand binds, an enzyme immediately inside the cell membrane o E.g. Atrial Natriuretic Peptide
is activated or inactivated
Intracellular Hormone Receptors
• Found inside the cell, either in the cytoplasm or nucleus
• Hormones that bind to these receptors are lipid-soluble
o Examples of these hormones include:
§ Adrenal and gonadal hormones
§ Thyroid hormones
§ Retinoid hormones
§ Vitamin D
o Readily diffuse through the cell membrane and bind to the receptors
• This type of receptor can only activate a gene response if:
o An appropriate combination of gene regulatory proteins is present
o Regulatory proteins are tissue-specific
• Hence, the responses of different tissues to a hormone are determined by:
o Specificity of the receptors




8 12
Gi: Inhibitory G protein MAPK: Mitogen-activated Protein Kinases
9 13
Gs: Stimulatory G protein PI3K: Phosphatidylinositol 3-Kinase
10 14
JAK: Janus Kinase cGMP: Cyclic Guanosine Monophosphate
11
STAT: Signal Transducer and Activator of Transcription

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o Expression of genes that the receptor regulates
Mechanism of Intracellular Hormone Receptors General Mechanism of Adenylyl Cyclase-cAMP

Figure 8. Intracellular Hormone Receptor Mechanism

1) Lipid-soluble hormones cross the cell membrane
Figure 9. The Adenylyl cyclase-cAMP Mechanism used by many hormones to
2) Hormone interaction with receptors in the cytoplasm or nucleus
exert their control on target cells
o Forms the activated hormone-receptor complex
3) The complex binds with the hormone response element, a specific 1) Hormone binds with receptor
promoter sequence in the target DNA 2) Coupling of receptor to a G protein
o This binding either promotes or inhibits gene transcription and mRNA o Gs protein à Stimulatory effect
synthesis o Gi protein à Inhibitory effect
4) Newly formed proteins are still present in the cell even after a long time 3) Gs protein stimulates adenylyl cyclase
has passed since the hormone has acted on the cell 4) Adenylyl cyclase catalyzes the conversion of cytoplasmic ATP into cAMP
o These proteins then control cellular functions 5) cAMP activates cAMP-dependent protein kinase
6) cAMP-dependent protein kinase phosphorylates specific cell proteins
C. SECOND MESSENGER SYSTEMS o These proteins trigger the biochemical reactions that ultimately lead to
cell’s response to the hormone
• Mediate intracellular hormonal functions

• Note that the only direct action of hormones is to activate a single type of
membrane receptor Cell Membrane Phospholipid
o Activation of this receptor in turn activates a “second messenger” • Hormones that use this second messenger system include:
• The second messenger is responsible for the subsequent steps of the o Angiotensin II (vascular smooth muscle)
biochemical cascade o Catecholamines (α receptor)
o Gonadotropin-releasing hormone
Adenylyl Cyclase-cAMP o Growth hormone-releasing hormone
o Parathyroid hormone
• Low concentrations of hormones acting on the cell can cause pronounced
o Oxytocin
effects
o Thyrotropin-releasing hormone
! Following cAMP formation, a few molecules of adenylyl cyclase can
o Vasopressin (V1 receptor, vascular smooth muscle)
activate many other enzymes subsequently activated in the cascade

• Intracellular cAMP concentration depends on whether the hormone
receptor couples with a stimulatory or inhibitory G protein
General Mechanism of Cell Membrane Phospholipid
o If the hormone receptor binds with a Gi protein à decreased
concentration of cAMP à decreased phosphorylation of key
intracellular proteins
! If hormone receptor bins with Gs protein, then vice versa happens
• The increase or decrease in cAMP concentration will induce
different actions in each type of target cell due to the unique nature of their
individual intracellular machinery
o e.g. Thyrocytes
§ cAMP stimulation will lead to the synthesis of thyroid hormones (T3
and T4)
o e.g. Tubular epithelial cells (Renal collecting tubules)
§ cAMP stimulation will increase their permeability to water
• Examples of hormones that use this second messenger system include:
o Adrenocorticotropic hormone
o Angiotensin II (epithelial cells)
o Calcitonin
o Catecholamines (β receptors)
o Corticotropin-releasing hormone
o Follicle-stimulating Hormone
o Glucagon
o Growth hormone-releasing hormone
o Human chorionic gonadotropin
o Luteinizing hormone Figure 10. The Cell Membrane Phospholipid Mechanism used by some
o Parathyroid hormone hormones to exert their control on target cells
o Secretin
o Somatostatin 1) Hormone binds with receptor
o Thyroid-stimulating hormone 2) Binding activates Phospholipase C
o Vasopressin (V2 receptor, epithelial cells) o Phospholipase C is attached to the inside projections of the receptors

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3) Phospholipase C catalyzes the breakdown of membrane phospholipids, Thyroid Hormones
15
especially phosphatidylinositol biphosphate (PIP2 ), into two second

messenger products:
16
o Inositol triphosphate (IP3 ) NOTE: The mechanism of action of the thyroid hormones are discussed in
th
2+
§ Liberates Ca ions from the mitochondria and endoplasmic length in Chapter 77 of Guyton and Hall Textbook of Medical Physiology 13
reticulum to exert effects including, but not limited to: Edition, hence, it is not described as a step-by-step process in this section.
Þ Smooth muscle contraction
Þ Cell secretion
o Diacylglycerol (DAG )
17 • Thyroxine (T4) and triiodothyronine (T3)
§ Activates Protein Kinase C • Increases transcription of specific genes in the nucleus by directly binding
Þ Protein kinase C phosphorylates specific cell proteins that trigger to nuclear receptors
biochemical reactions leading to the cellular response to the o These nuclear receptors are activated transcription factors within the
hormone chromosomal complex which control the function of gene promoters
§ Arachidonic Acid constitutes the lipid portion of DAG • Important functions in the nucleus:
Þ Precursor for the prostaglandins and other local hormones o Activates genetic machinery for the synthesis of 100 or more
intracellular protein types, majority of which are enzymes
o Can prolonged the effect of their functions (days to weeks) once bound
Calcium-Calmodulin to intranuclear receptors
2+
• Ca ions enter cells through calcium ion channels as a result of:
o Hormone binding with receptors
VII. MEASUREMENT OF HORMONE CONCENTRATIONS IN THE
o Changes in membrane potential
2+ -8 -7
• Normal Ca concentration in most cells: 10 to 10 mol/L
BLOOD
2+ -6 -5
o Ca concentration needs to increase to 10 to 10 mol/L to allow for • Most hormones in the blood are present in very minute quantities; thus,
sufficient binding with Calmodulin extremely sensitive methods should be used

General Mechanism of Calcium-Calmodulin A. RADIOIMMUNOASSAY
1) Hormone binds to a receptor or calcium channels open due to a change in • Revolutionized measurement of hormones, their precursors, and their end
membrane potential products
2) Calcium enters cell and binds with calmodulin o Extremely minute amounts of hormone can be assayed
o Calmodulin has four calcium-binding sites • The procedure is also performed for standard solutions of untagged
3) Calmodulin undergoes a conformational change if at least 3-4 sites are hormone at different concentrations
bound with calcium
4) Calmodulin activates or inhibits a calmodulin-dependent protein kinase Radioimmunoassay Procedure
5) Calmodulin-dependent protein kinase phosphorylates specific cell proteins
1) Antibodies highly specific for the hormone to be measured are produced
that trigger biochemical reactions leading to the cellular response to the
2) A small quantity of this antibody is mixed with fluid from the animal
hormone
containing the hormone of interest
o E.g. Myosin Light Chain Kinase
o The concentration of antibodies used must not be enough to
§ Acts on the Myosin of smooth muscles to induce contraction
completely bind the 2 hormone types introduced

3) This mixture is simultaneously combined with an appropriate amount of
D. DIRECT ACTION ON THE CELLULAR GENETIC MACHINERY purified standard hormone tagged with a radioactive isotope
o The hormone in the fluid and the radioactively tagged hormone will
compete for binding sites
NDTK: REMEMBER:
o The quantity of these two hormones that bind is proportional to its
• Steroid hormones à Protein synthesis
concentration in the assay fluid
• Thyroid hormones à Gene transcription
4) After reaching equilibrium, the antibody-hormone complex is separated

from the solution
Steroid Hormones 5) The quantity of radioactive hormone bound in this complex is measured by
radioactive counting techniques
• Causes synthesis of proteins in the target cells
6) A standard curve (Percent of antibody bound with radioactively tagged
o May function as enzymes, transport proteins, or structural proteins
hormone vs Concentration of the hormone to be measured in the test

sample) is plotted
General Mechanism of Steroid Hormones o Radioactive counts recorded from the sample are compared to that of
1) Steroid hormone enters the cytoplasm through diffusion and binds with a the standard curve to determine its hormone concentration
specific receptor protein
2) Receptor protein-hormone combination diffuses into or is transported into
B. ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
the nucleus
3) Receptor protein-hormone combination binds at specific points on the • Developed for accurate and high-throughput hormone measurements
DNA strands, which activates the transcription process of specific genes to • Can be used to measure almost any protein
form mRNA • Combines the features of antibody specificity and enzyme assay sensitivity
4) mRNA diffuses into the cytoplasm promoting translation at the ribosomes • Advantages:
to form new proteins o Does not use radioactive isotopes
o Can be automated
o Cost effective and accurate
EXAMPLE: ALDOSTERONE
• Enters the cytoplasm of renal tubular cells
• Binds to a mineralocorticoid receptor
• Eventually forms proteins at the ribosomes after about 45 minutes
• Acts primarily on the renal tubular cells to promote sodium reabsorption
and potassium secretion
• Secreted by the adrenal cortex

th
SOURCE: Guyton and Hall Textbook of Medical Physiology 13 ed., (p. 935)





15 17
PIP2: Phosphatidylinositol biphosphate DAG: Diacylglycerol
16
IP3: Inositol triphosphate

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ELISA Procedure HORMONE CLEARANCE
• METABOLIC CLEARANCE RATE: Rate at which a hormone is removed from
the blood
NDTK: IN SUMMARY
• AB1: bound to the well and first binds the hormone at a different binding MECHANISM OF ACTION OF HORMONES
site • RECEPTOR BINDING: A hormone first has to bind to highly-specific
• AB2: also binds the same hormone but at a different site receptors on the target cells for them to be able to exert their effects
• AB3: recognizes AB2 o HORMONE-RECEPTOR COMPLEX: What is formed when the hormone
• Enzyme: bound to AB 3; catalyzes the formation of a colored fluorescent binds to its receptor and directly precedes receptor activation
product from a substrate • INTRACELLULAR SIGNALING: Binding and consequent receptor activation
results to an intracellular signal transduction pathway

o ION CHANNEL-LINKED RECEPTORS: Receptors usually associated with
neurotransmitters that allow or prohibit the entry of ions into or out of
the cell
o GPCR: Receptors that indirectly regulate the activity of target proteins
by coupling with G proteins
§ G PROTEINS: Trimeric protein comprised of α, β, and γ subunits that,
depending on its configuration, may either be active or inactive
o ENZYME-LINKED RECEPTORS: Receptors that directly function as
enzymes when activated or are directly associated with enzymes that
they activate
§ JAK2: One of the pathways through which leptin receptor signaling
occurs
o INTRACELLULAR RECEPTORS: Receptors found on the cell cytoplasm or
nucleus

§ HORMONE RESPONSE ELEMENT: Specific sequence on the
Figure 11. Basic principles of ELISA promoter region of the target gene to which the hormone-receptor
complex binds
1) Each of the wells in a 96-well plastic plate is coated with an antibody (AB1)
• SECOND MESSENGER SYSTEMS
specific to the hormone being assayed
o ADENYLYL CYCLASE-CAMP: Involves the amplified synthesis of cAMP
2) Samples and standards are added to the wells
through the action of adenylyl cyclase to phosphorylate specific cell
3) A second antibody (AB2), which is also specific to the hormone but binds
proteins
to a different site, is added
o CELL MEMBRANE PHOSPHOLIPID: Involves the activation of
4) A third antibody (AB3), which recognizes AB2 and is coupled to an enzyme
Phospholipase C that splits membrane phospholipids into 2 secondary
which catalyzes the conversion a substrate to a colored fluorescent
messenger molecules, IP3 and DAG
product, is added 2+
§ INOSITOL TRIPHOSPHATE (IP3): Liberates Ca ions from the
5) The amount of the product, which is proportional to the amount of
mitochondria and endoplasmic reticulum
hormone, can then be measured using optical methods
§ DIACYLGLYCEROL (DAG): Activates Protein Kinase C

Þ ARACHIDONIC ACID: Precursor for the prostaglandins and other
QUICK REVIEW local hormones that constitutes the lipid portion of DAG
SUMMARY OF TERMS o CALCIUM-CALMODULIN: Controls the activity of calmodulin-
BASIC CONCEPTS & OVERVIEW dependent protein kinases that phosphorylate specific effector proteins
• NEUROTRANSMITTERS: Substances released by axon terminals of neurons as a result of the binding of calcium with calmodulin
into synaptic junctions which act locally to control neuronal functions • DIRECT ACTION ON THE CELLULAR GENETIC MACHINERY
• ENDOCRINE HORMONES: Substances released by glands or specialized
cells directly into the bloodstream that influence the function of distant MEASUREMENT OF HORMONE CONCENTRATIONS IN THE BLOOD
target tissues • RADIOIMMUNOASSAY: Method of measuring hormone concentrations by
• NEUROENDOCRINE HORMONES: Substances secreted by neurons directly tagging them with radioactive isotopes
into the bloodstream that influence the function of distant target tissues • ELISA: Method of measuring hormones that uses antibodies and the
• PARACRINES: Substances secreted by cells into the extracellular fluid and catalytic formation of a fluorescent product
affect neighboring target cells of a different type
• AUTOCRINES: Substances released into the extracellular fluid and act on SUMMARY OF PROCESSES
the same cell that produced them SYNTHESIS OF POLYPEPTIDE/PROTEIN HORMONES
• CYTOKINES: Peptides secreted by cells that can function as autocrines, 1) Synthesized first in the rough endoplasmic reticulum as larger proteins
paracrines, or endocrine hormones called preprohormones which are not biologically active
2) Preprohormones are cleaved to form prohormones
GENERAL CLASSES OF HORMONES 3) From the rough endoplasmic reticulum, prohormones are transferred to
• PROTEINS AND POLYPEPTIDES: Water-soluble hormones that comprise the Golgi apparatus for packaging into secretory vesicles
most of the hormone types in the body and are secreted via exocytosis 4) Enzymes in the vesicles cleave the prohormones to create biologically
• STEROIDS: Lipid-soluble hormones derived from cholesterol and consist of active hormones and inactive fragments
3 cyclohexyl rings and 1 cyclopentyl ring 5) Vesicles are either stored within the cytoplasm or bound to the cell
• AMINE HORMONES: Tyrosine derivatives formed by cytoplasmic enzymes membrane until secretion is needed
of glandular cells
SYNTHESIS OF STEROID HORMONES
HORMONE SECRETION 1) Hormonal stimulation of steroidogenic cells
• NEGATIVE FEEDBACK: Control mechanism for hormone secretion wherein 2) Hydrolysis of Cholesteryl Esters stored in lipid droplets to liberate free
the release of a hormone suppresses its further secretion Cholesterol
• POSITIVE FEEDBACK: Control mechanism for hormone secretion wherein 3) Sterol Carrier Protein-2 delivers Cholesterol from the cytoplasm to the
its release leads to the production of more hormones outer mitochondrial membrane
4) De novo synthesis of StAR
HORMONE TRANSPORT 5) StAR facilitates the translocation of Cholesterol from the outer to the inner
• WATER-SOLUBLE HORMONES: Hormones dissolved in plasma and carry mitochondrial membrane
out their functions in the target tissues by diffusing out of the capillaries 6) Cholesterol is converted to Pregnenolone by side chain cleavage
• LIPID-SOLUBLE HORMONES: Circulate in their bound form and cannot 7) Pregnenolone is further metabolized to form various steroids in the body
diffuse out of the capillaries to exert their actions unless they dissociate
from the plasma proteins

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SYNTHESIS OF THYROID HORMONES SECOND MESSENGERS: CALCIUM-CALMODULIN
1) Incorporated into the macromolecules of the protein thyroglobulin, which 1) Hormone binds to a receptor or calcium channels open due to a change in
are stored in large follicles within the thyroid gland membrane potential
2) When amines are split from thyroglobulin, the free hormones are released 2) Calcium enters cell and binds with calmodulin
into the blood stream 3) Calmodulin undergoes a conformational change if at least 3-4 sites are
3) Hormones bind to plasma proteins, especially thyroxine-binding globulin bound with calcium
4) They are then slowly released into the target tissues 4) Calmodulin activates or inhibits a calmodulin-dependent protein kinase
5) Calmodulin-dependent protein kinase phosphorylates specific cell proteins
SYNTHESIS OF CATECHOLAMINES that trigger biochemical reactions leading to the cellular response to the
1) Conversion of Tyrosine to L-Dopa hormone
2) Conversion of L-Dopa to Dopamine
3) Dopamine gets taken up into secretory vesicles MEASURING HORMONE CONCENTRATIONS: RADIOIMMUNOASSAY
4) Conversion of Dopamine to Norepinephrine 1) Antibodies highly specific for the hormone to be measured are produced
5) Conversion of Norepinephrine to Epinephrine 2) A small quantity of this antibody is mixed with fluid from the animal
6) Exocytosis of hormones containing the hormone of interest
3) This mixture is simultaneously combined with an appropriate amount of
INTRACELLULAR SIGNALING: ION CHANNEL-LINKED RECEPTORS purified standard hormone tagged with a radioactive isotope
1) Neurotransmitters bind to postsynaptic receptors 4) After reaching equilibrium, the antibody-hormone complex is separated
2) Binding causes a conformational change in the receptor, which usually from the solution
opens or closes a channel for one or more ions 5) The quantity of radioactive hormone bound in this complex is measured by
3) Altered movement of the ions through the channels causes subsequent radioactive counting techniques
effects on the postsynaptic cells 6) A standard curve (Percent of antibody bound with radioactively tagged
hormone vs Concentration of the hormone to be measured in the test
INTRACELLULAR SIGNALING: GPCR sample) is plotted
1) Binding of a hormone to the extracellular part of the receptor
2) The receptor undergoes a conformational change MEASURING HORMONE CONCENTRATIONS: ELISA
3) Activation of the GDP-bound G proteins 1) Each of the wells in a 96-well plastic plate is coated with an antibody (AB1)
4) Intracellular signal proteins alter the activity of ion channels or other specific to the hormone being assayed
intracellular enzymes 2) Samples and standards are added to the wells
5) Termination of signaling 3) A second antibody (AB2), which is also specific to the hormone but binds to
6) The α subunit combines with β and γ subunits to reform the inactive a different site, is added
membrane-bound trimeric G protein 4) A third antibody (AB3), which recognizes AB2 and is coupled to an enzyme
which catalyzes the conversion a substrate to a colored fluorescent
INTRACELLULAR SIGNALING: LEPTIN RECEPTORS product, is added
1) Leptin binding causes a receptor conformational change 5) The amount of the product, which is proportional to the amount of
2) Associated intracellular JAK2 molecules are phosphorylated and activated hormone, can then be measured using optical methods
3) Activated JAK2 molecules phosphorylate other tyrosine residues within the
leptin receptor-JAK2 complex EQUATIONS
4) Phosphorylation of STAT proteins
5) Activation of other enzyme systems (E.g. MAPK and PI3K) that mediate Equation 1. Metabolic Clearance Rate
physiological effects of leptin
𝑟𝑎𝑡𝑒 𝑜𝑓 𝑑𝑖𝑠𝑎𝑝𝑝𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑜𝑓 ℎ𝑜𝑟𝑚𝑜𝑛𝑒 𝑓𝑟𝑜𝑚 𝑝𝑙𝑎𝑚𝑎
𝑀𝑒𝑡𝑎𝑏𝑜𝑙𝑖𝑐 𝑐𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 𝑟𝑎𝑡𝑒 =
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑖𝑜𝑛 𝑜𝑓 ℎ𝑜𝑟𝑚𝑜𝑛𝑒
INTRACELLULAR SIGNALING: INTRACELLULAR RECEPTORS

1) Lipid-soluble hormones cross the cell membrane
2) Hormone interaction with receptors in the cytoplasm or nucleus REVIEW QUESTIONS
3) The complex binds with the hormone response element, a specific 1. Neuroendocrine hormones are secreted by cells into the _ to influence_.
promoter sequence in the target DNA a) Synaptic junctions; neighboring cells
4) Newly formed proteins are still present in the cell even after a long time b) Extracellular fluid; target cells at another location in the body
has passed since the hormone has acted on the cell c) Circulating blood; neighboring cells of a different type
5) These proteins then control cellular functions d) Circulating blood; target cells at another location in the body

SECOND MESSENGERS: ADENYLYL CYCLASE-CAMP 2. The following are characteristics of steroid hormones except:
1) Hormone binds with receptor a) Consist of 3 cyclohexyl rings and 1 cyclopentyl ring
2) Coupling of receptor to a G protein b) Water-soluble, allowing it to easily diffuse across cell membranes
3) Gs protein stimulates adenylyl cyclase c) Usually synthesized from cholesterol
4) Adenylyl cyclase catalyzes the conversion of cytoplasmic ATP into cAMP d) AOTA are correct
5) cAMP activates cAMP-dependent protein kinase
6) cAMP-dependent protein kinase phosphorylates specific cell proteins 3. T/F: Vesicles are only located along the cell membrane in preparation for
exocytosis.
SECOND MESSENGERS: CELL MEMBRANE PHOSPHOLIPID
1) Hormone binds with receptor 4. T/F: Catecholamines last longer in the blood than thyroid hormones.
2) Binding activates Phospholipase C
3) Phospholipase C catalyzes the breakdown of membrane phospholipids, 5. Which secondary messenger system is usually in play during the process of
especially phosphatidylinositol biphosphate (PIP2), into two second uterine smooth contraction?
messenger products IP3 and DAG a) Adenylyl Cyclase-cAMP
2+
4) IP3 liberates Ca ions, while DAG activates Protein Kinase C b) Cell Membrane Phospholipid
5) Protein Kinase C phosphorylates specific cell proteins that trigger c) Calcium-Calmodulin
biochemical reactions leading to the cellular response to the hormone d) cGMP

6. Which of the following is true?
a) DAG mobilizes calcium from the mitochondria
b) Intracellular cAMP concentration depends on whether the hormone
receptor couples with a stimulatory or inhibitory G protein
c) The increase or decrease in cAMP concentration will induce
similar actions in different target cells
d) Choice
e) IP3 activates protein kinase A

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7. T/F: Thyroid hormones increase protein synthesis.

8. Which antibody in ELISA is coupled to an enzyme which catalyzes the
conversion a substrate to a product?
a) AB1
b) AB2
c) AB3
d) ABO
e) ABC

9. When is the G protein-linked hormone receptors considered active?
a) When the GDP is exchanged with GTP
b) When 𝛼 , 𝛽, and 𝛾 subunits form a complex
c) When the cytoplasmic tail of the receptor dissociates from the 𝛼 , 𝛽,
and 𝛾 subunits form a complex
d) When the ligand doesn’t bind to the transmembrane receptor
e) All of the above

10. In intracellular hormone receptors, the ligand is able to enter the cell
because it is water soluble. The response of the cell that has these kinds of
receptors is only determined by the specificity of the receptors.
a) Only the first statement is true
b) Only the second statement is true
c) Both are true
d) Both are false

ANSWERS:
1D, 2B, 3F, 4F, 5B, 6B, 7F, 8C, 9A, 10D

EXPLANATIONS:
2. B. Water-soluble, allowing it to easily diffuse across cell membranes
– Steroid hormones are lipid-soluble.
3. F. – While many vesicles are located along the cell membrane, some are still
stored within the cytoplasm.
4. F. – Water-soluble hormones like catecholamines last a short time in the
blood.
5. B. Cell Membrane Phospholipid – Uterine smooth muscle is one of the
target sites of oxytocin, a hormone which uses the cell membrane
phospholipid second messenger system

REFERENCES
REQUIRED
& Hall, John E. Guyton and Hall Textbook of Medical Physiology.
Philadelphia, Elsevier Inc., 2016.
& Gardner, David G. & Shoback, Dolores. Greenspan’s Basic & Clinical
Endocrinology. McGraw-Hill Education, 2018.
2 ASMPH Batch 2023. 05/06/2019. 12.02: Molecular Biology of Hormones
& Action lectured by Anthony Harvey I. Aguilar, M.D.

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APPENDIX

APPENDIX A: Table 1. Endocrine Glands, Hormones, and Their Functions and Structure
CHEMICAL
GLAND/TISSUE HORMONES MAJOR FUNCTIONS
STRUCTURE
Thyrotropin-releasing
• Stimulates secretion of thyroid-stimulating hormone and prolactin Peptide
hormone
Corticotropin-releasing
• Causes release of adrenocorticotropic hormone Peptide
hormone
Growth hormone-releasing
• Causes release of growth hormone Peptide
hormone
Hypothalamus
Growth hormone inhibitory
• Inhibits release of growth hormone Peptide
hormone (somatostatin)
Gonadotropin-releasing
• Causes release of luteinizing hormone and follicle-stimulating hormone Peptide
hormone
Dopamine or prolactin-
• Inhibits release of prolactin Amine
inhibiting factor
Growth hormone • Stimulates protein synthesis and overall growth of most cells and tissues Peptide
Thyroid-stimulating • Stimulates synthesis and secretion of thyroid hormones (thyroxine and
Peptide
hormone triiodothyronine)
Adrenocorticotropic • Stimulates synthesis and secretion of adrenocortical hormones (cortisol,
Peptide
hormone androgens, and aldosterone)
Anterior pituitary Prolactin • Promotes development of the female breasts and secretion of milk Peptide
Follicle-stimulating • Causes growth of follicles in the ovaries and sperm maturation in Sertoli cells
Peptide
hormone of testes
• Stimulates testosterone synthesis in Leydig cells of testes
Luteinizing hormone • Stimulates ovulation, formation of corpus luteum, and estrogen and Peptide
progesterone synthesis in ovaries
Antidiuretic hormone • Increases water reabsorption by the kidneys
Peptide
Posterior pituitary (vasopressin) • Causes vasoconstriction and increased blood pressure
Oxytocin • Stimulates milk ejection from breasts and uterine contractions Peptide
Thyroxine (T4) and • Increases the rates of chemical reactions in most cells, thus increasing body
Amine
triiodothyronine (T3) metabolic rate
Thyroid
• Promotes deposition of calcium in the bones
Calcitonin Peptide
• Decreases extracellular fluid calcium ion concentration
• Has multiple metabolic functions for controlling metabolism of proteins,
Cortisol carbohydrates, and fats Steroid
Adrenal cortex • Has anti-inflammatory effects
• Increases renal sodium reabsorption, potassium secretion, and hydrogen ion
Aldosterone Steroid
secretion
Norepinephrine,
Adrenal medulla • Same effects as sympathetic stimulation Amine
epinephrine
• Promotes glucose entry in many cells, and in this way controls carbohydrate
Insulin (β cells) Peptide
Pancreas metabolism
Glucagon (α cells) • Increases synthesis and release of glucose from the liver into the body fluids Peptide
• Controls serum calcium ion concentration by increasing calcium absorption by
Parathyroid Parathyroid hormone Peptide
the guy and kidneys and releasing calcium from bones
• Promotes development of male reproductive system and male secondary
Testes Testosterone Steroid
sexual characteristics
• Promotes growth and development of female reproductive system, female
Estrogens Steroid
breasts, and female secondary sexual characteristics
Ovaries
• Stimulates secretion of “uterine milk” by the uterine endometrial glands and
Progesterone Steroid
promotes development of secretory apparatus of breasts
Human chorionic • Promotes growth of corpus luteum
Peptide
gonadotropin • Promotes secretion of estrogens and progesterone by corpus luteum
Human • Probably helps promote development of some fetal tissues, as well as the
Peptide
somatomammotropin mother’s breasts
Placenta
• Promotes growth and development of female reproductive system, female
Estrogens Steroid
breasts, and female secondary sexual characteristics
• Stimulates secretion of “uterine milk” by the uterine endometrial glands and
Progesterone Steroid
promotes development of secretory apparatus of breasts
Renin • Catalyzes conversion of angiotensinogen to angiotensin I (acts as an enzyme) Peptide
1,25-
Kidney • Increases intestinal absorption of calcium and bone mineralization Steroid
Dihydroxycholecalciferol
Erythropoietin • Increases erythrocyte production Peptide
• Increases sodium excretion by kidneys
Heart Atrial natriuretic peptide Peptide
• Reduces blood pressure
Stomach Gastrin • Stimulates hydrogen chloride secretion by parietal cells Peptide
Secretin • Stimulates pancreatic acinar cells to release bicarbonate and water Peptide
Small intestine
Cholecystokinin • Stimulates gallbladder contraction and release of pancreatic enzymes Peptide
• Inhibits appetite
Adipocytes Leptin Peptide
• Stimulates thermogenesis


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