Histochemical Demonstration of Δ5,3β-hydroxysteroid Dehydrogenase Activity in Cultured Leydig Cells under the Influence of Gonadotropic Hormones and Testosterone

The influence of gonadotropic hormones or testosterone upon activity of Δ⁵, 3β-hydroxysteroid dehydrogenase (Δ⁵,3β-OH-SDH) within cultured Leydig cells was histochemically investigated.
The following amounts of hormones were added into the culture medium: LH – 10, 100, 500, and 1000 ng/ml, FSH – 100 ng/ml, Testosterone (T) – 150 ng/ml of culture medium. Doses 10 and 100 ng LH stimulated the activity of the histochemically investigated enzyme, while 500 ng decreased enzyme activity and 1000 ng failed to support culture at all. FSH did not exert any influence on enzyme activity of cultured cells while testosterone decreased its activity beginning on day 6 in culture.     

Sperm Storage Capacity of the Indigenous West African Boar

The sperm reserves in the testis and epididymis of pubertal and adult indigenous West African boars were 4.22 and 4.99 times 10⁹ and 1.81 and 1.92 times 10⁹ respectively and were influenced by age and organ weight ( P < 0.05). Although these values were much less than those of exotic boars of about the same age, distribution in weights and sperm content of both indigenous and exotic boars is similar. However, testicular and epididymal sperm reserves were unrelated ( r = 0.19, P > 0.05) indicating that sperm storage capacity was still developing.     

Development of transmembrane signaling in the fetal rat Leydig cell

Gonadotropin binding to the adult Leydig cell activates a GTP binding protein that interacts with adenylate cyclase to increase cAMP production within the cell. The increased production of cAMP stimulates steroidogenesis and leads to an increase in testosterone production and secretion. The fetal Leydig cell responds to LH with an increase in cAMP and testosterone production as early as 15.5 days of gestation, although the specific mechanism of transmembrane signaling has not been characterized. Fetal rat testis cells from 13.5-20.5 days of gestation were treated with dibutyryl cAMP (dbcAMP), cholera toxin, and hCG to determine the onset of steroidogenesis stimulation by activation of each moiety in the transmembrane signaling system of the fetal Leydig cell. Maximal stimulation at each age from 14.5 through 20.5 days of gestation was achieved with 1 mM dbcAMP, 500 ng/ml cholera toxin, or 10 ng/ml hCG. At 13.5 days of gestation, fetal testes did not produce any testosterone. These findings indicate that a cholera toxin-sensitive, stimulatory guanine-nucleotide regulatory protein is functional in the fetal Leydig cell as early as 14.5 days of gestation. The LH receptor becomes functional in the transmembrane signaling system of the fetal Leydig cell at 14.5 days of gestation.     

Onset of steroidogenesis and differentiation of functional LH receptors in rat fetal testicular cultures

The present study was performed to investigate in vitro the onset of steroidogenesis and the responsiveness to LH in rat fetal testes. The male gonads explanted on days 12.5, 13.5, and 14.5 of gestation in M199 produced testosterone from 15.5 days as is the case in vivo dcAMP (1 mM) induced an anticipated steroidogenesis on day 14.5 with secretions of testosterone (0.026 +/- 0.003 ng/gonad/24 h) and progesterone (0.078 +/- 0.005 ng/gonad/24 h), whereas LH (100 ng/ml) has no effect. Antiandrogens such as aminoglutethimide (2 mM), cyproterone acetate (1 microgram/ml), and hydroxyflutamide (1 microgram/ml) could not delay the responsiveness to LH on day 15.5. An anticipated production of testosterone on day 14.5 in presence of DHA (200 ng/ml) could not induce functional LH receptors. It would appear that: (a) the onset of testosterone production occurs without extrinsic stimulatory factors; (b) dcAMP initiates an early steroidogenesis; (c) the onset of functional receptors is likely free of the androgenic environment.     

Testosterone and Testosterone Binding Globulin (TeBG) in Young Men during Prolonged Stress

The effect of prolonged physical and psychological stress on the testicular function was studied in 8 students (age 22–25 years) of the Norwegian Academy of War during a combat course of 5 days' duration. The average urinary excretion of free cortisol and 17-ketogenic steroids was 81 and 129% higher than the respective control values one week after the course. Plasma cortisol levels increased from 21.7 μg/100 ml at 8 a. m. before the course to 24.6 ( P < 0.05), and serum HGH rose from undetectable levels, < 0.08 ng/ml, to an average value of 12.9 ng/ml ± 3.7 (SD) at 8 a. m. during the course.
A marked suppressive effect on plasma testosterone levels from 5.6 ng/ml ± 1.4 to 0.9 ± 0.5, and no adjustment to stress was observed over a 5 day period. TeBG increased gradually from 26.9 nmol/l ± 9.9 to 52.7 ± 17.7 on day 6, followed by a slow decrease without reaching control values on day 12, suggesting that the decreased plasma testosterone levels probably reflect reduced production and not increased metabolism of testosterone. LH fluctuated during the course, but was significantly higher in the morning immediately following the end of the course than at the start ( P < 0.02). It is postulated that the effect of stress on the plasma testosterone levels is mediated via an action both on the hypothalamus-pituitary level and on the testis.     

Serum testosterone response to single injection of hCG ovine-LH and LHRH in male rats

A biphasic pattern of testosterone secretion in response to a single injection of 100 IU hCG has been observed in the rat. Serum testosterone increased from basal levels of 8.7 pL 3.1 ng/ml (mean pL SEM) to 23.0 pL 1.4 ng/ml within 2 h of hCG-stimulation and returned to control levels by 2 days. A second, delayed, but significant increase in serum testosterone occurred, reaching a peak of 24.6 pL 4.0 ng/ml at 3 days and declining to basal values at 5 days. To study this response further, lower doses of hCG were tried. Administration of 10 IU hCG produced a single peak of testosterone, which did not occur until 24 h. Differences in the serum testosterone response were related to the concentration of hCG measured in the serum after injection, as injection of 1 IU, which failed to increase serum hCG levels above detection, was also inadequate to increase serum testosterone. The response after stimulatin with 500 μg ovine-LH or 0.1–10.0 μg LHRH was also evaluated. Injection of 500 μg ovine-LH produced a significant rise in serum testosterone reaching a peak at 2 h of 25.2 pL 2.6 ng/ml and subsequently declining over the next 48 h to control levels where it remained for 5 days. Stimulation with doses of 0.1–10.0 μg LHRH produced rapid and short increases in serum LH concentration which induced peaks of testosterone up to 48.8 pL 14.1 ng/ml 1 h post injection. No secondary peak of testosterone followed. Failure of ovine-LH and LHRH to produce a second testosterone peak suggests that this response may be due to a re-stimulation of the Leydig cell by elevated levels of hCG which persist until the fourth day after injection.     

Sites of Action of Cyproterone and Cyproterone Acetate in the Immature Male Rat

Plasma testosterone (Leydig cell function), LH and FSH (pituitary function), the epididymal content of androgen binding protein (ABP) (Sertoli cell function) and plasma corticosterone (adrenal cortical function) were determined after 10 daily injections of varying doses of cyproterone and cyproterone acetate, beginning at 21 days of age. Daily doses of 0.5 mg or greater of either antiandrogen resulted in a marked depression in the levels of plasma testosterone and intra-testicular testosterone (measured only in the cyproterone group) with a dose-dependent decrease in testis and epididymal weights; both effects occurring with only minor changes in the levels of circulating gonadotrophins. In addition, these compounds caused a marked decrease in Sertoli cell secretion as reflected in a significant fall in the epididymal content of ABP.
A more detailed examination of the apparently direct effects of cyproterone on Leydig cell function revealed: 1) no major effects of in vivo treatment for 6 days (5 mg/day) on [I¹²⁵]hLH binding to testis membrane particles or on the in vitro response of enriched Leydig cell suspensions to hCG, 2) a dose-dependent inhibition of the hCG responsiveness of normal Leydig cells in the presence of the drug in vitro . The inhibitory effects on steroidogenesis in vivo can well be explained by a direct inhibition of the 3β-steroid-dehydrogenase-isomerase exerted by both antiandrogens.     

Developmental expression and androgen regulation of 24 kDa secretory proteins by the murine epididymis

Two peptides with a molecular weight of 24 kDa and a P _i of 8.4–8.8 were found to be synthesized and secreted specifically by the caput epididymis of adult male mice under androgen control. The peptides can interact with spermatozoa. In the present study, the developmental pattern of [³⁵S]-methionine-labelled proteins synthesized by the murine caput epididymis at 10, 20, 30 and 40 days of age were studied using two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and autoradiography. Active synthesis of the 24 kDa proteins was detected in the epididymis from 20 days of age, but secretion of the two peptides was only observed from 30 days of age onwards. To determine whether androgens influenced the active expression of 24 kDa proteins in the developing epididymis, their effect on [³⁵S]-methionine incorporation into proteins was assessed using 2D PAGE. Mice were either castrated, castrated then testosterone injected or simply testosterone injected at 10, 20, 30 or 40 days of age. Androgen control of 24 kDa protein expression was also studies in vitvo in epididymal organ culture over a 10-day period, with or without testosterone. Androgens were not involved in the initiation of synthesis of the 24 kDa proteins from days 10 to 20, as shown by in-vivo and in-vitro experiments. However, androgens appeared to be essential for maintaining synthesis and secretion of the proteins from 20 days of age onwards. Administration of excessive testosterone was only able to increase secretion of the 24 kDa proteins in intact male mice aged 40 days.     

Individual variation of hormonal recovery after cessation of luteinizing hormone-releasing hormone agonist therapy in men receiving long-term medical castration therapy for prostate cancer

OBJECTIVE: To evaluate the process of hormonal recovery after cessation of luteinizing hormone-releasing hormone (LHRH) agonist treatment in patients who had received long-term LHRH agonist therapy for prostate cancer. MATERIAL AND METHODS: Men who had successfully undergone androgen deprivation therapy with only monthly LHRH agonist therapy for > 30 months were enrolled and the administration of LHRH agonist was discontinued. Serum total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prostate-specific antigen (PSA) were measured before the cessation of LHRH agonist therapy and every 4 weeks thereafter, and the administration of LHRH agonist remained suspended until the total testosterone level recovered to > 50 ng/dl. RESULTS: Ten patients were enrolled in the study. The median (range) castration period and the levels of serum LH, FSH, total testosterone and PSA at cessation of therapy were 39 (30-56) months,<0.5 (<0.5-1.8) mIU/ml, 6.4 (3.0-15.9) mIU/ml, 15.3 (5.8-34.7) ng/dl and 0.13 (0.02-0.89) ng/ml, respectively. Testosterone recovered to > 50 ng/dl in all cases. There were large variations in the times required for recovery of LH and FSH (30-100 days) and serum testosterone (30-330 days). PSA began to increase at various testosterone levels, and there was a large variation (0-83%; median 41%) in the ratio of the androgen suppression (testosterone < 50 ng/dl) time to the period of LHRH agonist cessation. CONCLUSIONS: There was considerable variation in the hypothalamus-pituitary-testicular hormone profiles during recovery from long-term medical castration. These findings are noteworthy when interruption of androgen deprivation therapy is applied with the intention of delaying the progression of hormone-refractory cancer or improving the patient's quality of life.     

Effect of hyperprolactinemia and age on the hypogonadism of uremic men on hemodialysis

Primary hypogonadism has been commonly reported among uremic men on hemodialysis, characterized by low testosterone levels, increased luteinizing hormone and sometimes follicle-stimulating hormone levels. Little is known about the influence of hyperprolactinemia and age on this hypogonadism. In 149 hemodialysis patients and in 60 healthy subjects the serum levels of testosterone (T), gonadotropins (LH and FSH) and prolactin (PRL) were assessed through radioimmunoassay. Mean +/- SD hormone levels were: T 274 +/- 125 ng/100 ml, lower than controls; LH 44.7 +/- 46.1 mlU/ml and FSH 17.6 +/- 18.4 mIU/ml, both higher than controls. PRL 31.3 +/- 49.4 ng/ml, higher than controls. A positive correlation between LH and FSH, a negative correlation between PRL and both T and LH was found. Moreover T and FSH were correlated with age only in the normoprolactinemic patients. These data suggest: a common damaging mechanism by uremia on both interstitial and tubular structures of the testis; a central antigonadal influence of hyperprolactinemia even if a direct action on the testis cannot be excluded; a worsening action of age on the gonadal function of these patients.     

Evaluation of the effect of experimental cyclosporine toxicity on male reproduction and renal function. Reversal by concomitant human chorionic gonadotropin administration

Administration of cyclosporine to rats has been shown to impair testicular function, resulting in a decrease in sperm counts and fertility. In order to determine whether or not the deleterious effects of CsA could be reversed by hormonal therapy, mature male Sprague Dawley rats were treated with CsA (40 mg/kg/day, s.c.) alone or in combination with human chorionic gonadotropin (hCG) (5 micrograms/day/r; s.c.) for 14 days. Cyclosporine administration decreased the body weight (290 +/- 5.30 vs. 339 +/- 8.7 g; P less than 0.05) and reproductive organ weights (testis 1.49 +/- 0.42 vs. 1.60 +/- 0.03 g; epididymis 0.41 +/- 0.02 vs. 0.49 +/- 0.002 g; seminal vesicle 0.61 +/- 0.09 vs. 1.60 +/- 0.05 g; prostate 0.28 +/- 0.04 vs. 0.60 +/- 0.06 g; P less than 0.05) testicular sperm counts (5.80 +/- 0.42 vs. 8.49 +/- 0.48 x 10(7)/100 mg tissue; P less than 0.05) and epididymal sperm counts, (28.2 +/- 0.95 vs. 51 51.62 +/- 2.17 x 10(7)/100 mg tissue; P less than 0.05) and fertility (25% vs. 100%). Serum levels of LH were elevated (101.98 +/- 21.48 vs. 25.6 +/- 5.18 ng/ml; P less than 0.05) and testosterone was decreased (0.48 +/- 0.07 vs. 2.06 +/- 0.56 ng/ml; P less than 0.05). The administration of hCG to the CsA-treated rats restored the reproductive organ weights (testis 1.56 +/- 0.043 g; seminal vesicle 1.04 +/- 0.05 g; prostate 0.70 +/- 0.06 g) and sperm counts (testicular 7.88 +/- 1.0 x 10(7)/100 mg tissue; epididymal 59.86 +/- 4.16 x 10(7)/100 mg tissue; P less than 0.05) Serum levels of testosterone (18.63 +/- 4.45 ng/ml) and LH (431.65 +/- 31.41 ng/ml) were significantly elevated, as compared with control and CsA-treated groups (P less than 0.05). All the rats in the gonadotropin-treated group were fertile, as compared with 25% in the CsA-treated group. CsA reduced the kidney weight (1.17 +/- 0.02 vs. 1.27 +/- 0.03 g; P less than 0.05) and increased the levels of serum creatinine (0.97 +/- 0.07 vs. 0.59 +/- 0.03 mg/dl; P less than 0.05): these changes were ameliorated by the administration of hCG (kidney weight 1.35 +/- 0.03 g; creatinine 0.76 +/- 0.09 mg/dl).     

Hormone Profiles at High Altitude in Man

Altitude induced alterations in circulatory levels of PRL, LH, FSH and testosterone were studied in seven eugonadal men at sea level (SL), during their stay at high altitude (HA, 3500 m) and a week after return to SL. The mean plasma PRL level at SL was 5.83 +/- 1.7 SE ng/ml. On day one and seven of arrival at HA, the PRL values of 7.81 +/- 1.81 and 9.21 +/- 1.64 ng/ml respectively were not significantly different (p greater than 0.05) than the initial SL values. However, on day 18 of stay at HA, PRL levels were significantly increased (p less than 0.01) to 17.68 +/- 1.82 ng/ml and returned to initial SL values within seven days of return to SL. A significant decrease (p less than 0.01) in LH and testosterone was observed on seventh day of stay at HA and the decreased levels were maintained till day 18 of observations. Plasma testosterone returned to the initial SL values within a week of return to SL, whereas LH levels remained significantly lower (p less than 0.01). The FSH levels did not show any significant change during their stay at HA or after return to SL. These observations suggest that exposure to altitude is associated with hyperprolactenemia and an impaired pituitary gonadal function. The decreased levels of LH and testosterone at HA could either be due to hypoxic stress per se or secondary to altitude induced hyperprolactenemia.     

Effect of sodium arsenite on spermatogenesis,plasma gonadotrophins and testosterone in rats

To investigate the effect of arsenic on spermatogenesis. Methods: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg-kg^-day1 for 26 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), lutuneizing hormone (LH), testosterone and assessment of the epididymal sperm count. Results: In the 5 and 6 mg/kg groups, there were significant dose-dependent decreases in the accessory sex organ weights, epididymal sperm count and plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. The changes were insignificant in the 4 mg/kg group. Conclusion: Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone r     

Enhancement of Leydig cell testosterone secretion by isolated seminiferous tubules during co-perifusion in vitro: comparison with static co-culture systems

The aim of this study was to identify an in-vitro test system for the reproducible demonstration of a modulatory effect of isolated seminiferous tubules (s-tubules) on testosterone production by purified rat Leydig cells. Co-incubation of s-tubules with various numbers of Leydig cells had no significant effect on basal and hCG-stimulated testosterone production over 4-24 h incubation. In contrast, addition of s-tubule conditioned medium (STCM) to Leydig cells enhanced both basal and hCG-stimulated testosterone production over 5 h, but this effect was variable in magnitude and was not completely reproducible. Co-perifusion of isolated s-tubules with Percoll-purified Leydig cells for 6 h produced significant and consistent increases in Leydig cell testosterone secretion compared with Leydig cells perifused on their own. In six experiments, s-tubules enhanced Leydig cell testosterone secretion by 26 +/- 5% (P less than 0.001) in the absence of LH stimulation and by 48 +/- 11% following pulsatile stimulation with 1 ng/ml ovine LH (oLH). The presence of s-tubules enhanced (P less than 0.01-0.001) testosterone secretion by Leydig cells in response to pulses of oLH at doses ranging from 0.1 to 10 ng/ml, but the magnitude of enhancement was greatest with 0.1 and 1 ng/ml doses. These stimulatory effects were not explained by Leydig cell contamination or by testosterone leakage from the isolated s-tubules. Co-perifusion of Leydig cells with isolated epididymal tubules as a control tissue had no significant effect on LH-stimulated Leydig cell testosterone production. Stimulatory effects of s-tubules on Leydig cell testosterone secretion were observed at a 'physiological' ratio of s-tubules to Leydig cells (200 cm tubules/3 million cells) and was mediated by a humoural agent(s), since perifusion of s-tubules and Leydig cells in series gave similar results to co-perifusion of these tissues. This system proved to be robust and, in contrast to static culture systems, gave highly reproducible results, which should allow detailed investigation of the dynamic interactions between s-tubules and Leydig cells and the hormonal control of these events.     

Increased Serum FSH Levels Correlated with Low and High Sperm Counts in Male Infertile Patients

Serum FSH, LH and testosterone were measured in 57 (42) normal men and in 80 male infertile patients. In the former, mean (x) FSH was found to be 2.5 ng/ml with a range (x +/- 2 SD) from 0.25 ng/ml to 5.3 ng/ml, mean LH was 2.2 ng/ml with a range from 0.5 ng/ml to 5.6 ng/ml, and mean testosterone was 540 ng/100 ml with a range from 190 mg/ml to 890 ng/100 ml. Immunoassayable FSH was found to be elevated in 17 out of 42 presumably infertile males with sperm counts below 20 million/ml, and in 5 out of 12 men with sperm counts above 120 million/ml. There was no correlation between testosterone and sperm number, motility, and seminal fructose content. The concurrence of depressed spermatogenesis and elevated FSH levels seems to be a relatively good indicator for the presence of organic disorders of the testis.     

Effects of long-term testosterone administration on pituitary-testicular axis in end-stage renal failure

The endocrine effects of long-term testosterone administration were studied in 6 end-stage renal failure patients. During a 3-month control period where no androgens were administered the mean plasma testosterone level (7.3 nmol/l) was depressed while mean plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were elevated at 41.2 mU/ml, 105.5 mU/ml, and 63 ng/ml, respectively. These values were repeated during a 6-month study period where each subject was administered testosterone enanthate (400 mg) intramuscularly once a week. Plasma testosterone levels markedly increased in all subjects with a mean elevation of 72.4 nmol/l, while reductions were observed in FSH and LH levels with values of 2.7 and 16.3 mU/ml, respectively. When compared with control period values, these changes were statistically significant (p less than 0.05). Although the mean plasma PRL level of 49.0 ng/ml was reduced when compared with the control period values, this reduction was not statistically significant. Our control period findings of low plasma testosterone levels coupled with high plasma LH and FSH are consistent with Leydig cell dysfunction. The significant reductions in plasma FSH and LH noted during the study period indicate a negative feedback effect produced by the pharmacologic doses of testosterone. Long-term testosterone administration, however, did not significantly affect the elevated mean PRL levels observed in these subjects.     

ALTERATION OF THE HYPOTHALAMUS-PITUITARY-TESTIS AXIS IN OLIGOZOOSPERMIC MEN WITH NORMAL GONADOTROPIN LEVELS

Background:
Serum basal hormone levels such as lutenizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone, which is important to regulate testicular function, do not necessarily indicate the normal integrity of the hypothalamic-pituitary-testicular axis and the static measurement is not enough to detect the endocrine disorder. The dynamic measurement of gonadal hormone by GnRH test is considered to be more helpful to understanding the endocrine regulation of spermatogenesis. In this study, we performed GnRH test in oligozoospermic patients with normal levels of LH and FSH to examine the subtle alteration of hypothalamic-pituitary-testis axis.
Methods:
GnRH test was performed in 41 patients with oligozoospermia and normal gonadal hormone levels.
Results:
The responses of LH and/or FSH were excessive in most patients in spite of their normal gonadotropin levels. The patients with sperm concentration < 10 ± 10⁶/ml had significantly higher peak levels of both LH and FSH than did those with sperm concentration > 10 ± 10⁶/ml. In the patients with normal peak levels of both LH and FSH, sperm concentration was significantly higher than those with exceeded peak levels of FSH and/or LH after GnRH test. No significant differences were observed in estradiol, testosterone, free testosterone, or prolactin (PRL) levels between patients with normal responses and abnormal responses of LH and/or FSH.
Conclusions:
The feedback control of gonadotropin release from testis was worse in more severely oligozoospermic patients, although the precise mechanism of feed back still remains unknown.     

The pattern of LH release in the adult ram influences the testicular steroidogenic response to individual LH pulses and is regulated by testosterone negative feedback

Two experiments were conducted with adult intact rams (approximately 58 kg in body weight) in the nonbreeding season to investigate interrelationships between LH and testosterone secretion. In Experiment 1, LH pulse frequency was increased from approximately two to six peaks per 8 hours (for 56 hours) by injecting (iv) 10 micrograms NIH-LH-S18 every 80 minutes. Induction of a breeding season peak frequency produced a progressive 3-fold increase (P less than 0.01) in mean serum testosterone levels to values during the last 8 hours of treatment (12.6 +/- 1.2 ng/ml) that were 50% of those in the fall. In response to LH pulsing, testosterone peak amplitude increased (P less than 0.05) from 3.5 +/- 0.8 ng/ml to 6.7 +/- 0.7 ng/ml. In Experiment 2, the mean testosterone level was increased to breeding season values (for 96 hours) by injecting (im) 5 mg testosterone every 4 hours. Mean LH levels and LH peak frequency were decreased (approximately 70%, P less than 0.01) following 36 hours of treatment, and the LH response to exogenous GnRH was decreased (approximately 45%, P less than 0.01) by the final 4 hours Results indicate that for rams in the nonbreeding season, the testicular steroidogenic response to individual LH pulses is enhanced when pulse frequency is increased. When blood testosterone is elevated to breeding season levels, LH pulse frequency is severely impaired, while pituitary responsiveness to GnRH is diminished, as in the fall.     

Male hypogonadism of uremic patients on hemodialysis

Primary hypogonadism occurring among uremic men on hemodialysis has been widely investigated, yet few data are available concerning the general pattern of steroidogenesis. In 161 hemodialysis patients and in 83 healthy subjects, serum levels of gonadotropins (LH and FSH), prolactin (PRL), testosterone (T), androstenedione (A), estrone (E1), estradiol (E2), and dehydroepiandrosterone-sulphate (DHEA-S) were assessed through RIA methods. Mean +/- SD hormone levels were: LH 45.6 +/- 41.1 mIU/ml, FSH 16.3 +/- 16 mIU/ml, PRL 42.4 +/- 69.1 ng/ml, A 0.83 +/- 0.27 ng/ml, E1 64.3 +/- 31.7 pg/ml, all higher than controls; T 289 +/- 125 ng/100 ml, E2 11.8 +/- 3 pg/ml, and DHEA-S 1.4 +/- 1.4 micrograms/ml, all lower than controls. The A/T and E1/E2 ratios were also higher than controls and showed a good positive linear correlation (r = 0.40; p less than 0.001) between each other. The uremic damage acts at the testis level, impairing the activity of the enzyme 17-beta-hydroxysteroid-dehydrogenase (17-OHSD), even if a derangement of the peripheral interconversion between steroids cannot be excluded.     

Testosterone effects on luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the mouse

Studies in the mouse have demonstrated for the first time in vivo regulation of gonadotropin-releasing hormone (GnRH) on the minute-to-minute dynamics of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release and the effects of testosterone on this regulation. Intact and castrated mice with different testosterone levels (3-9 ng/mL) were challenged with exogenous GnRH while under general anesthesia to block endogenous GnRH release. Plasma concentrations of LH and FSH were determined by radioimmunoassay from sequential blood samples collected from anesthetized mice with in-dwelling catheters. The release of LH was correlated with the infusion of different doses of GnRH (0.35, 3.5, and 35 ng) in both intact and castrated mice (r = 0.942, approximately 0.999). GnRH-stimulated LH release was significantly lower in intact mice and in castrated mice with high testosterone levels than in castrated mice with low testosterone levels (P < .05). However, GnRH did not induce FSH release except in castrated males with low testosterone levels and at the highest dose of GnRH. The profiles of FSH release in intact mice and castrated mice with the highest testosterone levels were significant lower than the other groups (P < .05). In conclusion, release of LH, but not FSH, was correlated with increasing dosages of GnRH (r = 0.970), and testosterone significantly suppressed GnRH-stimulated LH release in the mouse (P < .05).