Testicular Capacity Research Articles

Physiological and histological study of the effect of finasteride drug (Prostacare) on the fertility of albino male rats

Their study was led to explore the impact of finasteride (Prostacare) on testicular capacity in Rattus Norvegicus. Forty five matured male rats with body weight of (200-300g) and (8) to (10) weeks of age were divided into (3) groups (15 rats/group). The first group was given orally with distilled water as acontrol and the others (second and third) were given orallywith two concentrations of finasteride (5mg /kg.b.w and 10mg /kg.b.w) daily for a period of (eight weeks). After the finish of the experiment ,rats was scarifiedfor the purpose of histological study and measurement of organs weights in the laboratory. The results showed a significant (p<0.05) decrease in the body, testis, epididymis and prostate gland weightsin compared with the control. Also the results of histological examination of testis and epididymis showed a significant (p<0.05) reduce in the seminiferous tubules diameters and reduction in number of the leydig’s cells, while there was a significant (p<0.05) rise in the interstitial spacebetween tubules compared to the control group.The results was showed necrosisin the seminiferous tubules of the testis.

Dynamic GnRH and hCG testing: establishment of new diagnostic reference levels.

Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after GnRH and hCG stimulation in healthy men and assess the impact of six single nucleotide polymorphisms on the responses. GnRH and hCG stimulation tests were performed on 77 healthy men, 18-40 years (reference group) at a specialized andrology referral center at a university hospital. The potential influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic-pituitary-gonadal axis. Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC-MS/MS. For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. Testosterone increased approximately 110% (range: 18.7-67.6 nmol/L) during hCG testing. None of the polymorphisms had any major impact on the test results. Results from GnRH and hCG tests in patients compared with the reference group showed that the stimulated level and absolute increase in LH showed superior identification of patients compared with the relative increase, and the absolute change in testosterone was superior in identifying men with Leydig cell insufficiency, compared with the relative increase. We provide novel reference ranges for GnRH and hCG test in healthy men, which allows future diagnostic evaluation of hypothalamic-pituitary-gonadal disorders in men.

The seasonal fertility of North American bison ( Bison bison) bulls

The objective of this study was to determine the presence and magnitude of seasonal fluctuations in semen quality and other reproductive indices in bison bulls. Testicles from 288 commercially slaughtered bison bulls were collected monthly over a 1-year period. Carcass and testicle weight were determined and measurements of seminiferous tubule lumen, diameter, and epithelial thickness were made. Sperm cell morphology and defects were described and quantified using epididymal semen from each testicle. Twenty-one Plains ( Bison bison bison) and Wood bison ( Bison bison athabascae) breeding bulls, averaging 6.0 years of age (range 2.5–8.0), from three farms were selected for semen collection and evaluation on the basis of producer co-operation. Semen was collected by electro-ejaculation on four seasonal occasions during a 12-month period. Ejaculate quality was judged on the basis of volume, density, gross and individual motility, morphology, live/dead ratio, and concentration. Sperm cell morphologies were evaluated microscopically and classified according to criteria used for bovine semen. Fecal testosterone was measured at each semen collection using a commercial competitive binding radioimmunoassay. There was an increase in carcass weights over the study period and testis weights were moderately correlated ( r = 0.44) with carcass weights. However, mean testes weights were heavier ( P < 0.05) in the summer than in winter, spring, or fall periods. There were no differences in the proportion of normal and abnormal epididymal sperm between seasons but there were seasonal changes in the testicular parenchyma. Seminiferous tubule and lumen diameter, and epithelial thickness were greatest ( P < 0.05) in summer. Live bulls gained weight between April and November, but lost weight over the winter. Normal sperm cell percentages as well as individual sperm cell motility in electro-ejaculated sperm samples were higher ( P < 0.05) at the pre-breeding collection relative to other collections, but no change in sperm cell concentrations occurred over the study period. Fecal testosterone concentrations were highest at the pre-breeding period (June) but decreased ( P < 0.05) in each subsequent collection to reach their lowest levels in the April. While many changes in seen characteristics were not significant, overall results indicate the presence of some reproductive seasonality and increased testicular capacity in the summer breeding season. Bulls showing marginal semen quality in the winter but otherwise carrying desirable genetic traits may warrant another evaluation in late spring prior to being culled from a breeding program.

Low Risk of Impaired Testicular Sertoli and Leydig Cell Functions in Boys with Isolated Hypospadias

Isolated hypospadias may result from impaired testicular function or androgen end-organ defects or, alternatively, from hormone-independent abnormalities of morphogenetic events responsible for urethral seam. The objective was to evaluate the relative prevalence of hormone-dependent etiologies in boys with isolated hypospadias. We studied endocrine testicular capacity in 61 patients with isolated hypospadias and 28 with hypospadias associated with micropenis, cryptorchidism, or ambiguous genitalia. Serum anti-Müllerian hormone and inhibin B were used as Sertoli cell markers. A human chorionic gonadotropin test was performed to evaluate Leydig cell function. Testicular dysfunction was observed in 57.1% and androgen end-organ defects in 7.2% of patients with hypospadias associated with cryptorchidism, micropenis, or ambiguous genitalia. In the remaining 35.7%, the disorder was idiopathic. The presence of ambiguous genitalia predicted the existence of testicular or end-organ dysfunction with 81.8% specificity. Isolated hypospadias was associated in 14.8% of patients with testicular dysfunction and in 6.5% of cases with end-organ defects; in 78.7% of cases, the condition was idiopathic. The occurrence of isolated hypospadias ruled out the existence of testicular or end-organ disorders with 80.0% sensitivity. Altogether our data indicate that the risk for the existence of an underlying testicular or end-organ dysfunction is low in patients with isolated hypospadias (odds ratio, 0.13; 95% confidence interval, 0.05-0.36; P < 0.001). Boys with isolated hypospadias are more likely to have normal endocrine testicular and androgen end-organ functions, suggesting that transient disruption of morphogenetic events in early fetal life may be the predominant underlying cause.

In vivo acute changes in ATP and glucose concentrations in the testicles of prepubertal rats following unilateral torsion

Objective: An experimental study has been conducted to investigate acute changes in testicular concentrations of ATP and glucose following one-hour unilateral 720° testicular torsion. Methods: Sixty prepubertal male Wistar rats were distributed into two groups. Group 1 (Ischemia) animals (n=30) were divided into 5 subgroups (n=6). All animals were subjected to right testicular torsion of 720° lasting one hour followed by detorsion. Testicles were collected and arterial blood samples taken from abdominal aorta at the end of ischemic period and 0.5, 1, 6 and 24 hours following detorsion. The remaining rats (Group 2 - Sham operated) were divided into 5 subgroups and submitted to a similar procedure but detorsion was performed immediately following torsion of the right testis. Results: ATP and glucose concentrations were significantly decreased (P&lt;0.05) in ischemia group as compared to sham group at the end of ischemic period. There was no difference in glycemia when comparing ischemic versus sham-operated rats. Conclusions: Unilateral one-hour testicular torsion causes a decrease in ipsilateral testicular perfusion resulting in decreased testicular concentrations of glucose and ATP. This finding suggests that one-hour unilateral testicular torsion impairs testicular capacity to produce ATP (energy) due to glucose storage depletion and reduced glucose uptake. Similar concentrations of glucose and ATP in testicular tissues of rats submitted to ischemia (Group 1) and sham-operated rats (Group 2) following detorsion implies the possible reversibility of these changes.

Growth hormone receptors in testis and liver during the spermatogenetic cycle in rainbow trout (Oncorhynchus mykiss).

Changes in growth hormone (GH) receptivity in the testis during the reproductive cycle were studied in rainbow trout (Oncorhynchus mykiss). This necessitated setting up a method to characterize GH receptors (GH-R) in crude testis homogenate. Binding of radiolabeled recombinant rainbow trout GH (125I-rtGH) to crude testis preparation was dependent on testicular tissue concentration. The sites were specific to GH, with no affinity for prolactins, gonadotropins, or insulin. Similar high affinities for 125I-rtGH were obtained with crude testis (4.5 x 10(9) + 0.25 M(-1)) and crude liver preparations (5.1 x 10(9) +/- 0.06 M(-1)) at all stages of spermatogenesis, as well as with testicular membrane preparations (2.4 x 10(9) M(-1)). GH-R concentration in testis was high during the immature stage (590 fmol/g testis); it then decreased regularly from the beginning (stage II, spermatogonia proliferation: 706 fmol/g testis) to the end of spermatogenesis (stage VII: 158 fmol/g testis). Conversely, the absolute testicular capacity increased dramatically between stages IV and VI (1.2-16.2 pmol/2 gonads), when testicular growth is extremely rapid. GH-R concentration in the liver was highest in early stages (6.5-6.7 pmol/g liver); this value then significantly decreased during midspermatogenesis (stage VI: 3.5 pmol/g liver) and returned to immature levels at the end of the cycle. No significant correlation was found between GH-R in testis, GH-R in liver, and plasma GH concentration. Preliminary experiments performed on isolated populations of testicular cells revealed that binding of 125I-rtGH was detectable in Sertoli cell-enriched fractions but not in germ cell populations. We conclude that GH-R are present in the testis during the entire reproductive cycle in rainbow trout, probably in somatic cells and in particular in Sertoli cells.

Effect of 17β-Estradiol, Testosterone, and 11-Ketotestosterone on 17,20β-Dihydroxy-4-Pregnen-3-One Production in the Rainbow Trout Testis

The principal hormone related to spermiation inOncorhynchus mykissis 17,20β-dihydroxy-4-pregnen-3-one (17,20βOHP). In the present study we analyzed the possible paracrine/autocrine effects of three other testicular steroids (17β-estradiol, 11-ketotestosterone, and testosterone) on the synthesis and secretion of this progestin in male rainbow trout. Pieces of testis at various stages of spermatogenesis were incubated for 24 or 48 hr with one of these steroids (5 to 800 ng ml−1) either alone or with the gonadotropin GtH II. Following incubation, 17,20βOHP was measured by RIA in the culture media.In vitro,only 17β-estradiol (E2) decreased 17,20βOHP secretion repeatedly and significantly when doses higher than or equal to 50 ng ml−1were used. This effect was observed mainly at the spermiating stage and under gonadotropic stimulation. In turn, E2 did not seem to modify the testicular capacity to convert 17-hydroxyprogesterone into 17,20βOHP.In vivo,the circulating levels of E2 decreased at the beginning of spermiation, concomitantly with an increase of 17,20βOHP in plasma. Thesein vitroandin vivodata suggest a possible role for E2 in the regulation of 17,20βOHP secretion by testes, in particular during the spermiating period.

Effect of finasteride on human testicular steroidogenesis.

We studied the testicular function and some androgen-mediated events in 22 males (16-30 years of age) with male pattern baldness that was treated with finasteride (10 mg once daily) for 2 years. Patients were evaluated every 3 months. Prostatic volume was determined in six subjects by endorectal ultrasound scans. Serum gonadotropin, prostate-specific antigen (PSA), and sex hormone levels were determined basally and periodically during the treatment period. Fourteen subjects underwent gonadal stimulation with human chorionic gonadotropin (hCG), and the gonadotropin response to gonadotropin releasing hormone (GnRH) was determined in eight subjects, prior to and after 2 years of therapy. Finasteride treatment resulted in an improvement in the male pattern baldness and prostatic shrinkage that was associated with an increase in serum testosterone levels (17.2 +/- 2.5 vs. 26.3 +/- 1.7 nmol/L) and a decrease in dihydrotestosterone (DHT) levels (1.45 +/- 0.41 vs. 0.38 +/- 0.10 nmol/L), causing a marked increase in that testosterone/DHT ratio. A significant increase in the serum levels of androstenedione (3.67 +/- 0.49 vs. 7.05 +/- 0.70 nmol/L) and estradiol (132 +/- 44 vs. 187 +/- 26 pmol/L) was also noted, whereas androstanediol glucoronide (33.3 +/- 6.4 vs. 10.7 +/- 4.5 pmol) and PSA (1.6 +/- 0.6 vs. 0.4 +/- 0.1 ng/ml) were significantly decreased. No changes in basal or stimulated levels of gonadotropin were observed. There was a significant increase in the testosterone response to hCG during finasteride therapy (delta: 16.7 vs. 35.5 nmol/L) that could be explained, at least in part, by the reduction of testosterone metabolism resulting from the blockage induced by finasteride. The decrease in the androstenedione to testosterone and estrone to estradiol ratios observed after hCG treatment, however, strongly suggests increased activity of the 17-ketosteroid reductase enzyme and an improvement of the testicular capacity for testosterone production.

GONADOTROPHIN‐RELEASING HORMONE AND HUMAN CHORIONIC GONADOTROPHIN TESTS REVEAL THAT BOTH HYPOTHALAMIC AND TESTICULAR ENDOCRINE FUNCTIONS ARE SUPPRESSED DURING ACUTE PROLONGED PHYSICAL EXERCISE

The mechanism of suppression of gonadotrophins and testosterone during prolonged exercise was studied. Fourteen healthy males were injected immediately before an exhaustive bicycle run for 4 h, and before a control period without exercise, with one of the following substances: (1) 1 ml of saline, (2) 100 micrograms of a GnRH agonist (buserelin), and (3) 50 IU/kg of hCG. Each test was repeated for each subject 2 weeks apart, in a randomized single-blind fashion. Blood samples were taken before the injections (sample A), 6 h after the injections (sample B), and the following morning (sample C). During placebo treatment testosterone concentration decreased from A samples to B samples more in the exercise trial than in rest trial (31 vs 8%, P = 0.02). This exercise-associated decrease was reversed by both the GnRH agonist and hCG treatments. Serum gonadotrophin concentrations responded identically to GnRH agonist injections during exercise and rest trials. hCG resulted in a greater increase of serum testosterone from A to C samples at rest than during the exercise trial (52 vs 33%, P = 0.04). In conclusion, the exercise-induced suppression of serum testosterone is associated with two effects: suppressed endogenous GnRH stimulation of gonadotrophin release during exercise, and decreased testicular capacity to secrete testosterone during recovery period.

Hormonal Regulation of Rat Testicular Arginine Vasopressin Receptors*

Previous studies have implicated arginine vasopressin (AVP) as a negative intratesticular modulator of androgen production. The present studies were undertaken to further define the testicular AVP system by investigating potential influences of pituitary hormones on testicular receptors for AVP. Binding of [3H]AVP to testicular membranes was time, temperature, and pH dependent, with optimum binding at 90 min, 22 C, and pH 8.0. Addition of divalent cations to the incubation mixture significantly increased binding by 4-, 10-, 15-, and 35-fold with Ca2+, Zn2+, Mg2+, and Mn2+, respectively. The influence of pituitary hormones on testicular AVP receptors was initially assessed by comparing binding parameters obtained by Scatchard analysis of saturation binding data between membranes prepared from intact or hypophysectomized rats. Testicular membranes from intact animals bound 66 +/- 2 fmol AVP/mg protein, whereas membranes from animals hypophysectomized 10 days previously showed a significantly lower binding capacity of 40 +/- 3 fmol AVP/mg protein; however, the affinity of the receptors for AVP did not differ between these two groups. A similar decrease was observed when binding was compared between purified Leydig cells isolated from intact and hypophysectomized animals by Metrizamide density gradients. Time-course analysis of this effect showed a continuous decline in total testicular AVP-binding capacity for the first 2 weeks after hypophysectomy and a slight increase at 3 weeks. Treatment of hypophysectomized animals with pituitary hormones beginning on the third day after hypophysectomy and continuing for either 4 or 7 days showed that LH and GH were able to dose-dependently restore testicular AVP-binding capacity to levels found in intact animals, whereas FSH and PRL were ineffective. These data indicate that testicular AVP receptors are under the control of LH and GH from the pituitary and suggest that pituitary hormones may impact on the efficacy of the testicular AVP system by regulating AVP receptor levels.

Pharmacological Studies on Androgen Suppression in Therapy of Prostate Carcinoma

In hormone-dependent prostate carcinoma, androgens can be suppressed into the castrate range by LHRH agonists. Testosterone secretion is blocked at two levels: testicular androgens and adrenal androgens. In humans, the contribution of testicular androgens is about 95%, whereas in the rat, the adrenal androgen secretion is negligible. Pharmacological studies were performed on the suppressive effect of the LHRH agonist, buserelin on androgen-dependent organs in adult rats. The reduction in pituitary and testicular binding capacity was monitored during treatment by injection, or by long-term infusion. Marked differences in suppressive mechanisms activated by the different regimens were observed. Changes in testicular steroid biosynthesis were analysed by incubation of testes after treatment with HCG, measuring the spectrum of C21/C19-steroids in incubation media. In particular, the levels of intraprostatic androgens were determined during treatment with daily buserelin injections, or with sustained release formulations of buserelin. The tissue content of testosterone and 5-alpha-dihydrotestosterone (DHT) were both markedly lowered. In castrate rats, stimulation of adrenal function by ACTH infusion had no effect on the prostate weight or intratesticular T/DHT content. Combination therapy during the initial phase of treatment by an androgen receptor blocker (cyproterone acetate) and buserelin (infusion or implants) was more effective to suppress prostate weight and intra-prostatic T/DHT content than therapy with the single compounds alone. Spermatogenesis and fertility were suppressed after prolonged treatment periods of 6-12 months; the testicular atrophy was not reversible in these long-term injection studies. Similar studies in dogs and monkeys have shown a different result: inhibition of spermatogenesis was fully reversible. It is concluded that studies on the mechanism of androgen suppression by LHRH agonists and the effects on androgen dependent organs provide useful information for the improvement in therapy of hormone-dependent prostate carcinoma.

The Effects of Tris(2,3-Dibromopropyl)Phosphate on the Reproductive System of Male Rats

Tris(2,3-dibromopropyl)phosphate (TRIS) administered intraperitoneally to adult, male Sprague-Dawley rats for 12 weeks at concentrations of 85.1 to 340.5 mg/week caused significant, dose-related declines in the weights of the testes, epididymides, and seminal vesicles. Sperm production by the testes and sperm storage in the epididymides were also reduced. Although prostate weight declined, the effect was not correlated with the dose of TRIS. Neither serum concentrations of testosterone nor the testicular capacity to produce testosterone in vitro were affected by any dose of TRIS.

Restoration effects of exogenous luteinizing hormone on the testicular steroidogenesis and Leydig cell ultrastructure.

In the present study, we explored the restoration effects of exogenous LH on Leydig cell ultrastructure and testicular steroidogenesis in rats that were deprived of endogenous LH via treatment with testosterone-17 beta-estradiol-filled Silastic implants for 10 days. Exogenous LH was supplied continuously via Alzet miniosmotic pumps at the rate of 1 microgram/h for 3, 6, 12, and 24 h or 1, 2, 4, 8, and 12 days. Testes were then perfused in vitro with medium containing 1) LH, 2) 20 alpha-hydroxycholesterol, or 3) pregnenolone substrate, which allowed us to assess LH-stimulated testosterone secretion, cholesterol side-chain cleavage activity, or the conversion of pregnenolone to testosterone, respectively. Other testes were perfusion fixed via the testicular artery for morphometric measurement of Leydig cell number and volume per testis and the surface area of Leydig cell cytoplasmic smooth endoplasmic reticulum (SER), inner mitochondrial membrane, and outer mitochondrial membrane. The results verified that Leydig cell smooth endoplasmic reticulum and inner and outer mitochondrial membrane surface areas are drastically diminished (P less than 0.05 vs. intact controls) by LH withdrawal. Also, the results verified that exogenous LH administered in situ restores Leydig cell ultrastructure and capacity to biosynthesize testosterone. However, the recovery of Leydig cell structure and steroidogenic reactions occurred at strikingly different rates upon restoration of LH after 10 days of the treatment with testosterone-17 beta-estradiol implants. For example, the restoration of testicular capacity to synthesize progesterone in response to LH stimulation or 20 alpha-hydroxycholesterol substrate was completed within 24 h. In contrast, the restoration of Leydig cell SER and testicular capacity to synthesize testosterone from pregnenolone was completed only after 8 days of continuous LH treatment (P greater than 0.05 vs. intact controls). Thus, our results show that LH rapidly restores Leydig cell post-LH receptor steroidogenic events up to and including cholesterol side-chain cleavage activity. Interestingly, there is no temporal association between the recovery of cholesterol side-chain cleavage activity and the surface area of inner mitochondrial membrane surface area. In contrast, 8 days are required to coincidentally restore SER surface area and the capacity of Leydig cells to synthesize testosterone from pregnenolone. We conclude that different cellular mechanisms are involved in the LH-dependent restoration of inner mitochondrial cholesterol side-chain cleavage activity and SER-associated conversion of pregnenolone to testosterone.

Effects of Gonadotropin-Releasing Hormone Receptor Blockade on Rat Testicular Gonadotropin and Lactogen Receptors, Steroidogenesis, and Responses to Human Chorionic Gonadotropin Stimulation*

Testicular endocrine regulation was studied in adult male rats after treatment with a potent GnRH antagonist analog [N-Ac-D-p-Cl-Phe1,2, D-Trp3, D-Lys6, D-Ala10-GnRH (Ant.)] given in doses of 1 mg/kg at 0, 12, and 24 h. One group of animals also received an injection of human CG (hCG) (600 IU/kg) at 12 h, and all animals were killed at 36 h for hormone and receptor (R) measurements. Treatment with Ant. blocked greater than 95% of the pituitary and testicular GnRH-R, and decreased serum LH concentration by greater than 90%. Testicular lactogen-R content was decreased by 60% (P less than 0.01), but there was no change in LH-R and FSH-R concentrations. Ant. decreased serum and testicular testosterone levels by 90%, and testicular capacity to produce testosterone in vitro by 50% (P less than 0.01). No decrease was observed in production rates of cAMP and progesterone. hCG alone abolished testicular LH-R, decreased lactogen-R by 55% (P less than 0.01), and GnRH-R by 65% (P less than 0.01). Desensitization of cAMP and testosterone production, and an increase in progesterone-testosterone ratio, were seen after hCG. hCG + Ant. treatment resulted in R, cAMP, and steroid responses that were indistinguishable from those seen after hCG alone. These findings indicate that: 1) Ant.-induced hypogonadotropism decreases testicular lactogen-R concentration and testosterone production; 2) testicular GnRH-R and lactogen-R are subject to heterologous down-regulation by hCG; and 3) inhibition of the putative GnRH-mediated regulation of testis by Ant. blockade of the GnRH-R does not change testicular response to hCG-treatment in vivo. Hence, the present observations still leave the physiological role of testicular GnRH-R open.

Chlordecone lacks estrogenic properties in the male rat

The reproductive toxicity of chlordecone has been hypothesized to derived from estrogen mimicry. To test this hypothesis, the effects of estradiol-17β, testosterone, and chlordecone on the male reproductive tract of 60-day-old male rats were compared after 72 days of exposure. Estradiol-17β (25 μg/week) and testosterone (945 μg/week), administered by polydimethylsiloxane capsules implanted subdermally, caused significant reductions in spermatogenesis, sperm motility, testicular capacity for secreting testosterone, and the weights of testes and epididymides. Estradiol-17β also caused significant declines in serum testosterone concentrations, and the weight of the prostate and seminal vesicles. Chlordecone, administered either by polydimethylsiloxane capsule or by ip injection, had no effect on any of these parameters, except to reduce significantly seminal vesicle weight at the highest dose of injected chlordecone, 7.5 mg/week. Therefore, chlordecone does not mimic estrogen in its effects on the reproductive system of the male rat.

EFFECT OF TREATMENT WITH AN AGONIST OF LUTEINIZING HORMONE RELEASING HORMONE ON EARLY MATURATIONAL CHANGES IN PITUITARY AND TESTICULAR FUNCTION IN THE RAT

Male rats aged 30 days were injected once daily for between 1 and 7 days with 50 ng (D-serine t-butyl6, des-glycine-NH210) luteinizing hormone releasing hormone ethylamide (LH-RH agonist), and pituitary and testicular function were assessed. Treatment for 7 days significantly (P less than 0.02) inhibited maturational increases in the pituitary content and serum concentration of gonadotrophins, testicular luteinizing hormone (LH)-receptor concentration and the testicular capacity to secrete testosterone; the pituitary content and serum concentration of prolactin, the hypothalamic content of LH-RH and testicular weight were unaffected. In rats treated with LH-RH agonist, the initial (2 to 3 days) reduction in testicular LH-receptors and the capacity to secrete testosterone probably resulted from acutely raised levels of LH in the blood, whilst later effects may have resulted from the apparently chronic reduction in serum gonadotrophin levels. The latter may reflect a decrease in pituitary responsiveness to repeated stimulation with LH-RH agonist. Despite the extensive loss of testicular LH-receptors and diminished responsiveness, the concentration of HCG which significantly (P less than 0.05) increased testosterone secretion by the testis in vitro was the same (2 pmol/l) as that for testes from control rats.

HYPOTHALAMIC, PITUITARY AND TESTICULAR FUNCTION DURING SEXUAL MATURATION OF THE MALE RAT

Hypothalamic content of gonadotrophin-releasing hormone (GnRH), serum LH and FSH, capacity of the testis to synthesize testosterone in vitro, and testicular 5-ene-3 beta-hydroxysteroid dehydrogenase-isomerase and 17 beta-hydroxysteroid dehydrogenase were measured in groups of rats at approximately 5 day intervals from birth to day 64 and at days 74 and 89. The capacity of the testes to synthesize testosterone in vitro was measured in the presence of a saturating dose of rat LH. Gonadotrophin-releasing hormone increased steadily from 0-17 ng per hypothalamus at birth to a maximum of 7 ng at day 52 and then remained constant. LH concentrations were highly variable and often exceeded adult values between days 10 and 32. After day 32 a steady rise was observed which reached adult values between days 37 and 42. FSH concentrations markedly increased from 255 ng/ml observed at birth and day 10 to a peak value of 1000 ng/ml at day 32. Subsequently there was a steady decline in FSH values until day 74 when the concentration returned to values found at birth. 5-ene-3 beta-Hydroxysteroid dehydrogenase-isomerase activity exhibited a rapid increase between days 12 and 19 followed by an even greater rate of increase between days 19 and 32 when adult levels were attained. 17 beta-Hydroxysteroid dehydrogenase activity was very low between birth and day 22. Enzyme activity began to increase at day 22 with a rapid increase in activity observed between days 37 and 58. The increase in capacity to synthesize testosterone closely followed the increase in 17 beta-hydroxysteroid dehydrogenase activity. The study demonstrates that during sexual maturation in the male rat, changes in serum LH and FSH do not reflect changes in hypothalamic GnRH. The appearance of Leydig cells as monitored by 5-ene-3 beta-hydroxysteroid dehydrogenase-isomerase activity precedes by approximately 20 days the increase in testicular capacity to synthesize testosterone in vitro. The latter coincides with the increase in 17 beta-hydroxysteroid dehydrogenase activity. These results suggest that 17 beta-hydroxysteroid dehydrogenase is a limiting factor in the ability of the testis to respond to LH stimulation.

Studies on the inhibition of fetal androgen formation: testosterone synthesis by fetal and newborn mouse testes in vitro.

The capacity of mouse testes to synthesize testosterone during fetal development, and the effects on synthesis of an inhibitor of 3- keto-4-steroid formation, 2α-cyano-4,4,17α-trimethyl- 17β-hydroxy-5-androsten-3-one (WIN) were studied. In fetal rats, WIN inhibited testicular 3 (3-hydroxy-5-steroid dehydrogenase activity and retarded development of the external genitalia (Goldman et al., Proc Soc Exp Biol Med 121: 757, 1966). Testes of fetal (14.5 and 17.5 days of gestation) and newborn mice from untreated mothers converted 4-14C-pregnenolone to 14C-testosterone during in vitro incubations. The results demonstrated testicular capacity for steroid metabolism to testosterone during the period of reproductive tract differentiation in mice. WIN, injected at doses of 1.5–7.0 mg/kg body weight into 12.5–15.5 day pregnant mice, exerted no effects on the gross development of the structures of the reproductive tract in either sex or on the conversion of 4-14C-pregnenolone to testosterone by fetal or newborn testes...

Effect of human chorionic gonadotropin on plasma concentrations of 17-hydroxycorticosteroids, dehydroepiandrosterone and androsterone in man.

ABSTRACT Following the administration of chorionic gonadotropin to normal human males, a significant increase in the concentration of plasma androsterone was demonstrated. This increase was not observed in 5 normal young females. After administration of chorionic gonadotropin the diurnal variation in the concentration of plasma dehydroepiandrosterone was nearly obliterated in normal male and female subjects. Minor variations in plasma 17-hydroxycorticosteroid levels were found in both sexes. It is suggested that the administration of chorionic gonadotropin with the subsequent measurement of plasma androsterone concentration may serve as a clinical test of testicular capacity in man.