The Endocrine system

The endocrine system forms part of the regulatory system of the body and works in conjunction
with the other regulatory mechanism, the nervous system.

Hormones
A series of endocrine glands secrete chemical messengers known as hormones, which are
carried by the blood to their target organs. These may be some distance away from the gland. In
contrast, exocrine glands produce secretions that are released via ducts and lie close to their
effector organs (e.g., sweat glands, gastric glands).
a. Characteristics
Chemically, hormones may be steroids, proteins or amines (derived from amino acids). They
regulate the activity of the target organ, which responds to that particular hormone. All other
organs are unaffected. The response produced by hormones is slower and lasts longer, and
complements the rapid and relatively short-lived responses produced by the nervous system.

b. Control of secretion
Hormonal secretion is controlled by different mechanisms (e.g., levels of a chemical in the
blood), or by a feedback loop. Secretion of a hormone occurs in response to a specific stimulus
(Table 1).
Table 1 Endocrine glands and their associated hormones
Stimuli may be:
• Nerve impulses: Adrenaline (epinephrine), for example, is released from the adrenal medulla
in response to nerve impulses from the sympathetic nervous system.
• A stimulating or releasing hormone, e.g., TSH, thyrotrophic/thyroid-stimulating hormone,
from the anterior pituitary gland activates the thyroid gland.
• Levels of certain chemicals in the blood, e.g., raised blood glucose levels, stimulate the
release of insulin from the pancreas.
• Feedback loops prevent oversecretion or reduce secretion once the effect has been achieved;
for example, oestrogen from the ovarian follicles prevents further secretion of follicle-
stimulating hormone from the anterior pituitary gland, so preventing further follicular
development.

Major endocrine glands

Fig. 1: Locations of important endocrine glands in the cat.

a. Hypothalamus
This small but vital region of the brain lies at the base of the brain and is connected by a “stalk”
to the pituitary gland and provides the link/ bridge between the nervous and endocrine
systems. It controls the autonomic nervous system, produces a range of hormones and
regulates the secretion of many others from the pituitary gland.
It is also an important centre for controlling the internal environment of the animal and
therefore maintaining homeostasis. For example, it helps regulate the movement of food
through the gut and the temperature, blood pressure and concentration of the blood. It is
also responsible for the feeling of being hungry or thirsty and it controls sleep patterns and
sex drive.

b. Pituitary
This is a small gland lying ventral to the hypothalamus in the forebrain (Fig. 1). It is also known
as the hypophysis and is divided into two lobes, each of which acts as a separate gland.
The pituitary gland is often referred to as the ‘master gland’ because its hormones control the
secretions of many of the other endocrine glands.
Anterior pituitary gland
Also known as the adenohypophysis, this produces:
• Thyrotrophic/thyroid stimulating hormone (TSH) stimulates the thyroid gland.
• Growth hormone or somatotrophin controls the rate of growth in young animals by:
○ Controlling the rate of growth at the epiphyses of the bones
○ Being involved in protein production from amino acids
○ Regulating the use of energy during periods of poor food supply. Glucose is conserved for use
by the nervous system and fat is broken down to be used as a source of energy by
the rest of the body.
• Adrenocorticotrophic hormone (ACTH) stimulates the adrenal cortex. Oversecretion may cause
the symptoms of Cushing’s disease.
• Prolactin stimulates the development of the mammary glands and the secretion of milk during
the latter half of pregnancy.
The milk cannot be released unless oxytocin is secreted at the end of the gestation period.
• Follicle stimulating hormone (FSH): At the start of the oestrous cycle, or at puberty, external
factors, such as day length (photoperiod), temperature or pheromones secreted by the male or
other females, affect the hypothalamus. This secretes gonadotrophin-releasing hormone, which
stimulates the anterior pituitary gland to secrete FSH. FSH stimulates germ cells in the ovary to
develop into follicles, each containing an ovum
(Fig. 2).
Fig. 2: Inter-relationships between the female reproductive hormones.
• Luteinising hormone (LH): Secretion is stimulated by the presence of oestrogen in the blood.
LH stimulates the ripe follicles in the ovary to rupture and release their ova (ovulation). The
remaining tissue becomes ‘luteinised’ to form the corpus luteum (Fig. 2).
• Interstitial cell stimulating hormone (ICSH) stimulates the interstitial cells or cells of Leydig in
the testis to secrete testosterone. This is the male equivalent of FSH.
Posterior pituitary gland
The posterior pituitary gland is also known as the neurohypophysis. The hormones associated
with this part of the pituitary gland are secreted by the hypothalamus and only stored here.
They are:
• Antidiuretic hormone (ADH), also called vasopressin, alters the permeability of the collecting
ducts of the kidney to water. It is secreted in response to the changing volume of extracellular
fluid (ECF) and helps maintain homeostasis.
• Oxytocin has two effects:
○ It acts on the mammary glands during late pregnancy and causes the milk to be released or
‘let down’ in response to suckling by the neonate.
○ At the end of gestation, oxytocin causes the contraction of the smooth muscle of the uterus,
resulting in parturition and delivery of the fetuses.
Diabetes insipidus: This presents as polydipsia, polyphagia and production of urine with a
specific gravity of around 1.00 (normal SG in the dog is 1.018–1.045). The condition may be a
result of undersecretion of ADH from the posterior pituitary gland or failure of the renal tissue
to respond to the hormone that controls the concentration of urine in the renal collecting ducts.
Diagnosis is confirmed by the water deprivation test and treatment relies on the daily
administration of ADH drops, which may not always be obtainable.

c. Thyroid
These lie in the midline on the ventral aspect of the first few rings of the trachea (Fig. 1). They
are controlled by TSH from the anterior pituitary gland and secrete three hormones:
• Thyroxin (or T4) and tri-iodothyronine (or T3) have a similar effect. Tri-iodothyronine contains
a high proportion of the trace element iodine; a lack of iodine in the diet can have a dramatic
effect. Both hormones affect the uptake of oxygen by all the cells in the body and are essential
for normal growth.
• Calcitonin lowers the levels of blood calcium by decreasing the rate of bone resorption. When
levels of blood calcium are high (e.g., if a calcium-rich diet is eaten), calcium is deposited in the
bone and acts as a reservoir for later use (Fig. 3). Calcitonin has an opposite effect to
parathormone but is of less importance.

Fig. 3: Control of blood calcium levels by calcitonin and parathormone.

Undersecretion of thyroid hormones – hypothyroidism – is more common in dogs. In young
animals, hypothyroidism causes dwarfism (stunted growth). In older animals, the condition is
known as myxoedema: the dog becomes fat and sluggish, alopecic, the skin feels cold and
clammy and the heart rate slows, all due to a reduced metabolic rate.
Oversecretion –hyperthyroidism –more common in old cats. The affected animal is thin, active,
often aggressive, has a good appetite and a fast heart rate, all due to a raised metabolic rate.
d. Parathyroid
These glands lie on either side of the thyroid gland and secrete the hormone parathormone
(Fig. 1). Secretion is dependent on the levels of calcium in the blood. If levels are low, calcium is
resorbed from the bones and absorption of calcium from the intestine is increased (Fig. 3).
Oversecretion (hyperparathyroidism) occurs in:
• Primary hyperparathyroidism, due to neoplasia of the parathyroid glands. This causes bone
resorption, bone weakness and pathological fractures.
• Secondary hyperparathyroidism, as seen in chronic renal failure. The calcium: phosphate ratio
in the blood is altered by impaired kidney function. This leads to increased output of
parathormone and consequently increased resorption of bone in an effort to maintain blood
calcium levels. There is preferential resorption from the mandible and maxilla, producing a
condition known as ‘rubber jaw’ – the jaw becomes pliable and fragile and the teeth may fall
out.
• Nutritional hyperparathyroidism results from low-calcium diets (e.g., an all-meat diet).
Parathormone is produced in an attempt to raise the blood calcium levels by bone resorption.

e. Adrenal
There is a pair of adrenal glands, one lying close to the cranial pole of each kidney (Fig. 1). Each
gland has an outer cortex and an inner medulla. There is no connection between
the two parts and they can be considered as two separate glands.
Adrenal cortex
The hormones produced are known as steroids and have a similar structure based on lipid.
There are three groups, each one being secreted by a different layer:
• Glucocorticoids: Secretion is regulated by ACTH from the anterior pituitary gland. The
hormones are known as corticosteroids; the most important are cortisol and corticosterone. In
the normal animal they are present in low levels but increase in response to stress. They have
two main actions:
○ They increase blood glucose levels by reducing glucose uptake by the cells, increasing the
conversion of amino acids to glucose in the liver (a process known as gluconeogenesis) and
mobilizing fatty acids from the adipose tissue ready for conversion to glucose.
○ When present in large quantities, they depress the inflammatory reaction, which delays
healing and repair. This property is used therapeutically to reduce swelling and inflammation.
• Mineralocorticoids: The most important is aldosterone. This acts on the distal convoluted
tubule of the kidney where it regulates acid–base balance of the plasma and ECF by excretion of
H+ ions and also controls the excretion of Na+ and K+ ions.
• Adrenal sex hormones: Both male and female animals produce all types of sex hormones.
They are secreted in insignificant quantities but may be the reason why some animals show a
certain level of sexual behaviour despite being neutered.
Cushing’s disease is caused by oversecretion of glucocorticoids, or hyperadrenocorticism. The
clinical signs include polydipsia, polyuria, polyphagia, bilateral symmetrical alopecia, muscle
wasting and a potbelly. The condition may result from oversecretion of ACTH from the anterior
pituitary gland or from a tumour of the adrenal cortex. Treatment involves the removal of the
neoplastic adrenal gland or suppression of the secretion of adrenocortical hormones by drugs
such as trilostane.
Adrenal medulla
This produces two hormones with similar actions: adrenaline (epinephrine) and noradrenaline
(norepinephrine). These hormones prepare the body for emergency action, known as the ‘fear,
flight, fight’ syndrome, and are controlled by the sympathetic nervous system. Their actions are
to:
• Raise blood glucose levels by the breakdown of glycogen stored in the liver – glycogenolysis.
This increases the body’s energy levels.
• Increase the heart rate and the rate and depth of respiration; this increases the amount of
oxygen reaching the tissues.
• Dilate the blood vessels of the skeletal muscles; this enables the supply of glucose and oxygen
to reach the areas where it is needed.
• Decrease the activity of the gastrointestinal tract and the bladder. In an emergency their
functions are less important.

f. Pancreas
The pancreas is a pinkish lobular gland lying in the loop of the duodenum in the abdominal
cavity (Fig. 1). It has an exocrine part and an endocrine part and is described as being a mixed
gland. The exocrine secretions, which are digestive juices, enter the duodenum via the
pancreatic duct. The endocrine secretions are produced by discrete areas of tissue within the
exocrine tissue, known as the islets of Langerhans.
The islets of Langerhans secrete three hormones, each from a different type of cell:
• Insulin (from the beta cells) is secreted in response to high blood glucose levels. Insulin lowers
blood glucose levels by:
○ Increasing the uptake of glucose into the cells, where it is metabolised to provide energy
○ Storing excess glucose as glycogen in the liver. Conversion of glucose to glycogen occurs by a
process known as glycogenesis (Fig. 4).
Fig. 4: Control of blood glucose levels
• Glucagon (from the alpha cells) is secreted in response to low blood glucose levels. Glucagon
raises blood glucose levels by breaking down the glycogen stores in
the liver. Conversion of glycogen to glucose occurs (Fig. 4).
• Somatostatin (from the delta cells) is mildly inhibitory to the secretions of insulin and
glucagon and prevents wild fluctuations in blood glucose levels, which may damage the tissues.
It also decreases gut motility and the secretion of digestive juices, which serve to reduce the
efficiency of the digestive and absorptive processes.

Diabetes mellitus: This results from a lack of insulin and is a condition in which the animal
suffers from hyperglycaemia and glucosuria (the presence of glucose in the urine). If left
untreated, the condition may progress to a stage where the body uses its protein and fat stores
as a source of energy. Daily insulin injections and dietary control are necessary to control the
condition.

g. Gonads
The ovary
Female mammals have two ovaries, which lie one on each side of the dorsal abdominal cavity
caudal to the kidneys. At the onset of sexual maturity, the two ovaries become capable of
secreting two hormones:
• Oestrogen is produced by the walls of the developing ovarian follicles. Development of germ
cells in the ovary into ripe follicles is the result of the secretion of FSH from the anterior
pituitary gland. Oestrogen causes the behaviour associated with the oestrous cycle and
prepares the reproductive tract and external genitalia for mating. Oestrogen also exerts
negative feedback on the anterior pituitary gland, preventing further secretion of FSH and
further follicular development (Fig. 5).
Fig. 5: Inter-relationships between the female reproductive hormones.

• Progesterone is secreted by the corpus luteum, which develops from the remaining follicular
tissue after the follicle has ovulated. The corpus luteum develops as a result of the production
of LH from the anterior pituitary gland. Progesterone prepares the reproductive tract for
pregnancy and maintains the pregnancy. During pregnancy, progesterone exerts negative
feedback on the hypothalamus and prevents secretion of gonadotrophin- releasing hormone
and so prevents further oestrous cycles until parturition occurs. It also causes development
of the mammary glands during pregnancy (Fig. 5).
In the later stages of pregnancy, the corpus luteum also secretes a hormone known as relaxin.
This causes the sacroiliac and other ligaments around the birth canal to soften and relax in
preparation for parturition.
False or pseudopregnancy and pyometra are two conditions of the entire bitch that may result
from the prolonged high levels of progesterone secreted by the corpus luteum of the bitch.
The corpus luteum normally remains for about 42 days, which is much longer than in any other
mammal. High levels of the hormone may cause a pregnancy-like state in some bitches, or in
older individuals reduces the speed of the inflammatory response, resulting in failure to
eliminate bacteria that may invade the uterine tissue, leading to the accumulation of pus and
the absorption of bacterial toxins.
The testis
Male mammals possess a pair of testes, which are carried external to the abdominal cavity
within the scrotum. At the start of sexual maturity, the testes begin to secrete two hormones:
• Testosterone is produced by the interstitial cells or cells of Leydig in response to the secretion
of ICSH from the anterior pituitary gland. Testosterone is responsible for:
○ The development of male characteristics such as penis development, development of the
barbs on the feline penis, muscle development, jowls on the face of a tomcat, size
○ Male behaviour patterns, such as sexual drive, aggression, territorial behaviour, courtship
displays and mating behaviour
○ Development of spermatozoa
• Oestrogen is produced in small quantities by the Sertoli cells in the seminiferous tubules of the
testes.
Sertoli cell tumour is a condition affecting older dogs or dogs with retained testes. The Sertoli
cells proliferate and secrete high levels of oestrogen, resulting in feminization syndrome. The
clinical signs are bilateral symmetrical alopecia, gynaecomastia (enlarged mammary glands) and
attractiveness to male dogs. The treatment is to castrate the patient.

h. Other endocrine organs

1) Kidney
The kidneys produce three important hormones: erythropoietin, calcitriol (1,25-
dihydroxycholecalciferol) and renin. They also synthesize prostaglandins, which affect many
processes in the kidneys.
In addition to synthesis, the kidneys also contribute to the degradation of certain hormones –
such as insulin (forms insulinase – cleaves insulin) or parathyroid hormone.
Erythropoietin
Erythropoietin is a peptide hormone which regulates erythropoiesis.
Structure and function
Erythropoietin is a glycoprotein containing 165 amino acids. Its receptors are present on the
membranes of red blood cell precursors. Binding of the hormone reduces apoptosis of these
cells – multiple cells survive and can therefore complete their development into mature
erythrocytes.
Final activation of vitamin D to the active hormone calcitriol takes place in the kidneys – 1-
hydroxylation of 25- hydroxycholecalciferol to 1,25- dihydroxycholecalciferol.
Calcitriol stimulates the small intestine for protein synthesis allowing absorption of Ca2+ and
phosphates. This ensures the availability of Ca2+ and phosphate for bone growth. Calcitriol
simultaneously activates osteoblasts to synthesize collagen.
Renin
Renin is part of the renin – angiotensin – aldosterone system (RAAS)
In the case of insufficient blood flow to the kidneys (e.g., decrease in blood volume) cells of the
renal juxtaglomerular apparatus begin the synthesis of protein renin. Renin is an enzyme, which
catalyzes the conversion of plasmatic angiotensinogen to angiotensin I. Angiotensin I is then
converted by angiotensin converting enzyme to angiotensin II, which stimulates aldosterone
synthesis and causes vasoconstriction.
2) Stomach
The lining of the stomach, the gastric mucosa, produces a hormone, called gastrin, in response
to the presence of food in the stomach. This hormone stimulates the production of hydrochloric
acid and the enzyme pepsin, which are used in the digestion of food.

3) Small intestine
The mucosa of the small intestine secretes the hormones secretin and cholecystokinin. Secretin
stimulates the pancreas to produce a bicarbonate-rich fluid that neutralizes the stomach acid.
Cholecystokinin stimulates contraction of the gallbladder, which releases bile. It also stimulates
the pancreas to secrete digestive enzyme.

4) Placenta
The placenta develops in the pregnant female as a source of nourishment and gas exchange for
the developing fetus. It also serves as a temporary endocrine gland. One of the hormones it
secretes is human chorionic gonadotropin, which signals the mother's ovaries to secrete
hormones to maintain the uterine lining so that it does not degenerate and slough off in
menstruation.

5) Thymus
Thymosin, produced by the thymus gland, plays an important role in the development of the
body's immune system.

6) Pineal
The pineal gland is found deep within the brain. It is sometimes known as the ‘third eye” as it
responds to light and day length. It produces the hormone melatonin, which influences the
development of sexual maturity and the seasonality of breeding and hibernation. Bright light
inhibits melatonin secretion Low level of melatonin in bright light makes one feel good and this
increases fertility. High level of melatonin in dim light makes an animal tired and depressed and
therefore causes low fertility in animals.

i. Prostaglandins
Prostaglandins are a group of physiologically active lipid compounds (cyclic fatty acids) called
eicosanoids having hormone-like effects in animals. They have impact on ovarian, uterine,
placental, and pituitary function to regulate reproduction in female livestock. They play
important roles in ovulation, luteal function, maternal recognition of pregnancy, implantation,
maintenance of gestation, microbial-induced abortion, parturition, postpartum uterine and
ovarian infections, and resumption of postpartum ovarian cyclicity. Prostaglandins have both
positive and negative effects on reproduction; they are used to synchronize oestrus, terminate
pseudopregnancy in mares, induce parturition, and treat retained placenta, luteinized cysts,
pyometra, and chronic endometritis.