ABSTRACT Summary A new method of radioimmunoassay (RIA) for serum estriol (E3) which utilizes125I... more ABSTRACT Summary A new method of radioimmunoassay (RIA) for serum estriol (E3) which utilizes125I-estriol as a tracer has been developed. This steroid was radioiodinated with chloramine T and purified by Sephadex LH-20 column chromatography. Two hundred and sixty-two samples from 130 normal pregnant patients at different stages of gestation were analysed. From 5 women, blood samples were drawn at 15 min intervals for 1 h. An increase in the circulating levels of E3 was observed throughout normal pregnancy and the results were widely distributed. The episodic fluctuations of E3 showed a variation of 13–20 ng/ml during the same 1-h sampling period. The quality control results showed the viability of this RIA in the determination of serum E3 utilizing the iodinated steroid as a tracer.
The control of androgen production by the Leydig cell is dependent upon the episodic secretion of... more The control of androgen production by the Leydig cell is dependent upon the episodic secretion of hormone (LH), which is released from the anterior pituitary gland in pulses of high biological activity. This mode of episodic LH secretion supports steroidogenic enzyme activity in the testis through interaction with LH receptors and stimulation of the adenylate cyclase/protein kinase sequence, leading to phosphorylation of key intermediates in the steroid biosynthetic pathway. The plasma membrane events that are rapidly activated by the specific interaction of LH or hCG with Leydig cell receptors include increased binding of guanyl nucleotide, and stimulation of cAMP-independent, Ca2+-dependent phosphorylation of a 44,500 Mr protein, with the characteristics of the adenylate cyclase nucleotide regulatory unit. Hormonal activation of adenylate cyclase is affected by Ca2+ with the same concentration-dependence, suggesting that nucleotide-induced phosphorylation is related to activation of the catalytic cyclase unit. In addition to the characteristic increases in pregnenolone synthesis and androgen production, gonadotropin-stimulated Leydig cells show prominent changes in LH receptor content and steroidogenic activity that modify their subsequent responses to hormonal signals. Thus, after exposure to increased LH and hCG levels in vivo and in vitro, LH receptors show an initial transient increase (up-regulation) followed by a marked decrease (down-regulation) and a prolonged depletion of LH receptor sites. Large doses of hCG cause "early" (prior to pregnenolone) and "late" steroidogenic lesions (17 alpha-hydroxylase, 17-20 desmolase) that are independent of receptor loss. The early lesion is partly due to reduced activity of HMG CoA reductase, and is mainly attributable to the increased activity of an inhibitory protein factor that modulates the activity of cholesterol side chain cleavage enzyme in Leydig cell mitochondria. In contrast, the late steroidogenic lesion is related to the nuclear actions of E2 produced during hormonal action. After hCG stimulation, an increase in nuclear E2 binding was accompanied by an early rise of RNA polymerase activities within 45 min coincident with the maximal increases in circulating testosterone and estradiol levels. These events were followed by the emergence of an E2-induced protein of Mr 27,000 at 3-6 h, and by reduction in the activity of 17 alpha-hydroxylase/17-20 desmolase, and a decrease in microsomal cytochrome P-450.(ABSTRACT TRUNCATED AT 400 WORDS)
Gonadotrophin-releasing hormone (GnRH) antagonists may have a future role in the control of canin... more Gonadotrophin-releasing hormone (GnRH) antagonists may have a future role in the control of canine reproductive function. In this study, the effects of a single dose of the potent GnRH antagonist, acyline, on serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were evaluated in male dogs. Blood samples were drawn before (Day -1) and after (30, 60, and 90 min, 3, 6, 9, 12, and 24h, and 3, 6, 9, 14, 22, and 29 d) treatment with acyline (330 microg/kg, sc); serum concentrations of FSH, LH, and T varied throughout the study period (P<0.01, <0.05, and <0.01, respectively). Gonadotrophins decreased below pretreatment concentrations 60 min after injection, whereas T took 90 min to decrease below baseline (P>0.05). Follicle-stimulating hormone, LH and T decreased until Day 9, when they reached their nadir at 2.0 +/-1.1 ng/mL (P<0.01), 1.2+/-0.2 ng/mL (P>0.05), and 0.5+/-0.2 ng/mL (P<0.05), respectively. Both gonadotrophins and T began increasing on Day 14 after treatment, although FSH and T serum concentrations still remained below baseline on that day (P>0.05). Follicle-stimulating hormone and T rebounded above baseline on Day 29, whereas LH reached concentrations were similar to baseline at this time (P>0.05). No local or systemic side effects were detected in any dog following acyline treatment. In conclusion, a single acyline treatment safely and reversibly decreased serum gonadotrophin and T concentrations in dogs for 9 d.
Serum radioimmunoassayable testosterone (T), cortisol and luteinizing hormone (LH) were determine... more Serum radioimmunoassayable testosterone (T), cortisol and luteinizing hormone (LH) were determined before and after dexamethasone (DXM) administration in 35 patients with idiopathic hirsutism (IH). Blood samples were taken at 15-min intervals during 1 hour in both basal and post-DXM conditions. Testosterone values obtained in 5 normal women in the same conditions during the early follicular phase were (mean +/- SD): baseline, 2.26 +/- 0.49 nmol/l; post-DXM, 0.80 +/- 0.35 nmol/l. Serum T levels in the whole group of patients with IH were significantly higher than those in the control group (mean +/- SD): baseline, 3.30 +/- 1.80nmol/l; post-DXM, 1.67 +/- 1.49nmol/l. Patients with IH were divided into 4 groups according to T results in the DXM test (mean +/- SD in both basal and post-DXM conditions, respectively): group 1 (n = 13) 1.67 +/- 0.66 and 0.62 +/- 0.35nmol/l; group 2 (n = 11) 3.89 +/- 1.63 and 3.09 +/- 1.49nmol/l; group 3 (n = 6) 3.96 +/- 1.46 and 0.87 +/- 0.73nmol/l; and gro...
Information on the effect of abnormal thyroid function on male reproduction is less available tha... more Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 fig GnRH plus 200 fig thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 ± 4.7 vs. 5.0 ± 1.9 mlU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 ± 3.4 and 12.0 ± 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 ± 0.8 and 3.1 ± 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.
ABSTRACT Summary A new method of radioimmunoassay (RIA) for serum estriol (E3) which utilizes125I... more ABSTRACT Summary A new method of radioimmunoassay (RIA) for serum estriol (E3) which utilizes125I-estriol as a tracer has been developed. This steroid was radioiodinated with chloramine T and purified by Sephadex LH-20 column chromatography. Two hundred and sixty-two samples from 130 normal pregnant patients at different stages of gestation were analysed. From 5 women, blood samples were drawn at 15 min intervals for 1 h. An increase in the circulating levels of E3 was observed throughout normal pregnancy and the results were widely distributed. The episodic fluctuations of E3 showed a variation of 13–20 ng/ml during the same 1-h sampling period. The quality control results showed the viability of this RIA in the determination of serum E3 utilizing the iodinated steroid as a tracer.
The control of androgen production by the Leydig cell is dependent upon the episodic secretion of... more The control of androgen production by the Leydig cell is dependent upon the episodic secretion of hormone (LH), which is released from the anterior pituitary gland in pulses of high biological activity. This mode of episodic LH secretion supports steroidogenic enzyme activity in the testis through interaction with LH receptors and stimulation of the adenylate cyclase/protein kinase sequence, leading to phosphorylation of key intermediates in the steroid biosynthetic pathway. The plasma membrane events that are rapidly activated by the specific interaction of LH or hCG with Leydig cell receptors include increased binding of guanyl nucleotide, and stimulation of cAMP-independent, Ca2+-dependent phosphorylation of a 44,500 Mr protein, with the characteristics of the adenylate cyclase nucleotide regulatory unit. Hormonal activation of adenylate cyclase is affected by Ca2+ with the same concentration-dependence, suggesting that nucleotide-induced phosphorylation is related to activation of the catalytic cyclase unit. In addition to the characteristic increases in pregnenolone synthesis and androgen production, gonadotropin-stimulated Leydig cells show prominent changes in LH receptor content and steroidogenic activity that modify their subsequent responses to hormonal signals. Thus, after exposure to increased LH and hCG levels in vivo and in vitro, LH receptors show an initial transient increase (up-regulation) followed by a marked decrease (down-regulation) and a prolonged depletion of LH receptor sites. Large doses of hCG cause &quot;early&quot; (prior to pregnenolone) and &quot;late&quot; steroidogenic lesions (17 alpha-hydroxylase, 17-20 desmolase) that are independent of receptor loss. The early lesion is partly due to reduced activity of HMG CoA reductase, and is mainly attributable to the increased activity of an inhibitory protein factor that modulates the activity of cholesterol side chain cleavage enzyme in Leydig cell mitochondria. In contrast, the late steroidogenic lesion is related to the nuclear actions of E2 produced during hormonal action. After hCG stimulation, an increase in nuclear E2 binding was accompanied by an early rise of RNA polymerase activities within 45 min coincident with the maximal increases in circulating testosterone and estradiol levels. These events were followed by the emergence of an E2-induced protein of Mr 27,000 at 3-6 h, and by reduction in the activity of 17 alpha-hydroxylase/17-20 desmolase, and a decrease in microsomal cytochrome P-450.(ABSTRACT TRUNCATED AT 400 WORDS)
Gonadotrophin-releasing hormone (GnRH) antagonists may have a future role in the control of canin... more Gonadotrophin-releasing hormone (GnRH) antagonists may have a future role in the control of canine reproductive function. In this study, the effects of a single dose of the potent GnRH antagonist, acyline, on serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were evaluated in male dogs. Blood samples were drawn before (Day -1) and after (30, 60, and 90 min, 3, 6, 9, 12, and 24h, and 3, 6, 9, 14, 22, and 29 d) treatment with acyline (330 microg/kg, sc); serum concentrations of FSH, LH, and T varied throughout the study period (P&lt;0.01, &lt;0.05, and &lt;0.01, respectively). Gonadotrophins decreased below pretreatment concentrations 60 min after injection, whereas T took 90 min to decrease below baseline (P&gt;0.05). Follicle-stimulating hormone, LH and T decreased until Day 9, when they reached their nadir at 2.0 +/-1.1 ng/mL (P&lt;0.01), 1.2+/-0.2 ng/mL (P&gt;0.05), and 0.5+/-0.2 ng/mL (P&lt;0.05), respectively. Both gonadotrophins and T began increasing on Day 14 after treatment, although FSH and T serum concentrations still remained below baseline on that day (P&gt;0.05). Follicle-stimulating hormone and T rebounded above baseline on Day 29, whereas LH reached concentrations were similar to baseline at this time (P&gt;0.05). No local or systemic side effects were detected in any dog following acyline treatment. In conclusion, a single acyline treatment safely and reversibly decreased serum gonadotrophin and T concentrations in dogs for 9 d.
Serum radioimmunoassayable testosterone (T), cortisol and luteinizing hormone (LH) were determine... more Serum radioimmunoassayable testosterone (T), cortisol and luteinizing hormone (LH) were determined before and after dexamethasone (DXM) administration in 35 patients with idiopathic hirsutism (IH). Blood samples were taken at 15-min intervals during 1 hour in both basal and post-DXM conditions. Testosterone values obtained in 5 normal women in the same conditions during the early follicular phase were (mean +/- SD): baseline, 2.26 +/- 0.49 nmol/l; post-DXM, 0.80 +/- 0.35 nmol/l. Serum T levels in the whole group of patients with IH were significantly higher than those in the control group (mean +/- SD): baseline, 3.30 +/- 1.80nmol/l; post-DXM, 1.67 +/- 1.49nmol/l. Patients with IH were divided into 4 groups according to T results in the DXM test (mean +/- SD in both basal and post-DXM conditions, respectively): group 1 (n = 13) 1.67 +/- 0.66 and 0.62 +/- 0.35nmol/l; group 2 (n = 11) 3.89 +/- 1.63 and 3.09 +/- 1.49nmol/l; group 3 (n = 6) 3.96 +/- 1.46 and 0.87 +/- 0.73nmol/l; and gro...
Information on the effect of abnormal thyroid function on male reproduction is less available tha... more Information on the effect of abnormal thyroid function on male reproduction is less available than that for the female. To assess the effects of hyperthyroidism on hypothalamic-pituitary-testicular axis and on spermogram parameters, 25 male patients (19-47 years old) suffering from active Graves' disease were studied. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL) were measured before and after administration of 100 fig GnRH plus 200 fig thyrotropin-releasing hormone (TRH). Testosterone (T), estradiol (E2), and 17-hydroxyprogesterone (17-OHP) were determined before and after 5000 IU human chorionic gonadotropin (HCG) administration. Serum sex hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), androstenedione and bioavailable testosterone (bioT), and bioavailable estradiol (bioE2) were also measured. Spermograms according to World Health Organization (WHO) criteria were determined in 21 patients. Hormonal and seminal studies were repeated in six patients after 7 to 19 months of euthyroidism achieved after treatment for hyperthyroidism. As a control group, 10 normal men were evaluated. Impaired sexual function, gynecomastia, and low testicular volume were found in 12, 6, and 3 hyperthyroid patients. Mean basal LH was significantly higher than the control group (7.8 ± 4.7 vs. 5.0 ± 1.9 mlU/mL, respectively, p < 0.02), with hyperresponse to GnRH. The response of PRL to TRH was lower in patients versus control group (30 minutes: 3.9 ± 3.4 and 12.0 ± 2.8 ng/mL, p < 0.01). Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T). The maximal increment of T and 17-OHP after HCG was lower in hyperthyroid patients than in normal men (p < 0.019 and p < 0.001, respectively). Basal bioT was lower in patients than controls (1.7 ± 0.8 and 3.1 ± 1.9 ng/mL, p < 0.02). The following incidence of abnormal semen parameters was found: asthenospermia 85.7%, hypospermia 61.9%, oligospermia 42.9%, necrospermia 42.9% and teratospermia 19.0%. In euthyroidism, a normalization of 85% of seminal alterations was observed in the limited number of patients evaluated. Our results confirm that hyperthyroidism causes marked alterations of the gonadotropic and PRL axis and dramatically affects spermatic function. BioT measurement was useful to identify hypoandrogenism in these patients in spite of the high concentration of total testosterone. The restoration of most semen parameters when euthyroidism was achieved suggests that the alterations were induced by the Graves' disease.
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