Effect of Androgens on Antipyrine Metabolism in the Rabbit

The inactivation of endogenous steroids and foreign compounds by the liver hydroxylative pathway, can be modified by androgenic substances. The inhibitory or inductory activity, can be estimated by measuring the half-life of antipyrine. Androgens (testosterone propionate, 5α-dihydro-testosterone and mesterolone) reduce antipyrine metabolism in male rabbits. In females, androgens are not inhibitors, but one of them, 5α-dihydrotestosterone, shows an inductive effect on liver oxidative mechanisms.     

Effects of gonadotrophin treatment in vivo on testicular function in immature rhesus monkeys (Macaca mulatta)

Changes in testicular histology and concentrations of testosterone and oestradiol 17β in testicular tissue and plasma have been studied following administration of gonadotrophins (oFSH, oLH, hCG and PMSG) to immature male monkeys. Treatment with FSH (1 mg/day) or PMSG (100 IU/day) for five days, induced a marked enlargement of the seminiferous tubules and increase in the Sertoli cell cytoplasm. Injections of LH (1 mg/daily) or hCG (100 IU/daily) administered similarly, failed to produce hypertrophy of the Sertoli cell. In LH, hCG and PMSG stimulated testes morphologically differentiated interstitial cells could be recognized. FSH did not produce any detectable effect on the intertubular tissue. A significant increase in testicular and plasma testosterone levels was observed with LH, hCG and PMSG. FSH was shown to be much less effective in stimulating androgenesis. An increase in testicular oestradiol production over that of controls, was observed in FSH and PMSG treated monkeys but not in animals treated with LH or hCG.     

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.     

Effect of continual light deprivation and alpha-2u-globulin replacement therapy on serum concentration of gonadotropins and testicular activity in rats

Summary. Prolonged darkness caused a fall in testicular 17 β-hydroxysteroid dehydrogenase (17β-HSD) activity and diminished spermatogenesis, serum levels of gonadotropins, testosterone and α_2u-globulin.
Administration of α_2u-globulin at a dose of 1.5 mg rat⁻¹ per day for 7 days after 68 days of light deprivation, reversed the 17β-HSD activity and serum levels of gonadotropins, testosterone and α_2u-globulin, while spermatogenesis was restored to normal.
The animals kept in prolonged darkness for 68 days and then received saline (7 days in light-dark cycle, 14 L: 10 D), showed no significant changes of testicular activity, serum levels of gonadotropins, testosterone and α_2u-globulin, when compared with dark-exposed animals (68 days) receiving rabbit serum (7 days in light-dark cycle, 14 L: 10 D). These results suggest that α_2u-globulin plays an important role in testicular function in dark-exposed rats by inducing gonadotropins and testosterone secretion.     

Basal serum testosterone as an indicator of response to clomiphene treatment in human epididymis,seminal vesicles and prostate

The present study was designed to determine the response of human epididymis, seminal vesicles and prostate function after a 5-day course of clomiphene citrate in men attending an infertility service. In 45 men, the secretions of the epididymis, seminal vesicles and prostate were assessed by measurements of seminal alpha-glucosidase, fructose and acid phosphatase, respectively. Subjects were classified as normal or abnormal: abnormal men were defined as those who either had history of a sexually transmitted disease (STD), leukocytospermia, hypoandrogenism, or a low response of Leydig cells to clomiphene stimulation; and normal subjects were those who did not have these conditions. Mean serum testosterone luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly increased after the short course with clomiphene citrate. After clomiphene citrate stimulation, the men in the normal group showed significantly increased marker levels of the seminal vesicles (P < 0.02) and prostate (P < 0.05), but not of the epididymis (P : NS). Men classified as abnormal showed no response according to the markers of the seminal vesicles and epididymis. Men with history of STD and abnormal basal values of acid phosphatase did not respond to the treatment. Men with history of STD but normal basal values of seminal acid phosphatase increased significantly in their levels of seminal acid phosphatase after clomiphene stimulation (P < 0.02). Multivariate analysis showed that the basal serum testosterone level was the only variable in predicting the probability of response to the clomiphene in terms of true-corrected seminal fructose, seminal acid phosphatase and seminal alpha-glucosidase levels. In fact, a high response of the seminal vesicles was observed in men with the highest basal serum testosterone levels (0.45 +/- 0.17; coefficient of regression +/- standard error; P < 0.018). However, a high response in terms of seminal acid phosphatase (P < 0.004) or alpha-glucosidase (P < 0.037) was observed in men with low basal serum testosterone levels. In conclusion, in the normal men, true-corrected fructose and acid phosphatase but not alpha-glucosidase in semen increased after duplicate androgen stimulation. An absence of response was observed in cases with history of STD/leukocytospermia or hypoandrogenism.     

Testosterone and 5α-dihydrotestosterone Concentrations in Human Seminal Plasma

Testosterone and dihydrotestosterone (DHT) were estimated by radioimmunoassay in human seminal plasma. Testosterone concentrations showed no significant differences between fertile and infertile semen samples, whereas DHT concentrations were significantly lower in azoospermic and oligozoospermic samples. It is concluded that testosterone derives essentially from the accessory sex glands, whereas DHT is mainly of testicular or epididymal origin. The low DHT concentrations found in seminal plasma of oligozoospermic and azoospermic patients is probably due to defective epididymal conversion of testosterone to DHT.     

Effect of α-chlorohydrin on metabolism and testosterone secretion by rat testicular interstitial cells

The direct effect of alpha-chlorochydrin (alpha-CH) on basic metabolism (glucose utilization and oxygen consumption) and testosterone secretion by isolated rat interstitial cells (I-cells) has been studied. In the range of concentrations between 5 and 100 microliter/ml, only the highest doses of alpha-CH decreased cell vitality and their histochemical stain for 3 beta-HSD. Oxygen consumption of I-cells was depressed at all doses higher than 10 microliter/ml and this effect was reversible only with doses lower than 50 microliter/ml. glucose utilization by I-cells was depressed significantly by alpha-CH and this effect was particularly dramatic with doses higher than 50 microliter/ml. alpha-CH decreased testosterone secretion by I-cells, with maximal effects at 100 microliter/ml. I-cells responded to hCG challenge by increasing testosterone secretion, and hCG prevented the toxic effect of alpha-CH at the lowest dose (10 microliter/ml) of alpha-CH, but failed to overcome the effects of a high dose (100 microliter/ml).     

Influence of age and photoperiod on steroidogenic function of the testis in the golden hamster

The golden (Syrian) hamster is a seasonal breeder, and exposure of adult animals to short days results in severe gonadal regression with morphological features that resemble the immature testis. The purpose of this study was to investigate testicular steroidogenic capacity in the golden hamster and to analyse the influence of age and photoperiod on this process. Hamsters aged 36 days were maintained on a long photoperiod (14L:10D), and adult animals were then exposed to a long or a short photoperiod (6L:18D) for 14 weeks (the period of time required to achieve maximal gonadal regression), to assess circulating levels and in vitro production of testosterone, dihydrotestosterone and androstane-3 alpha, 17 beta-diol. In peripubertal hamsters, androstane-3 alpha, 17 beta-diol was the main circulating androgen detected, whereas in active adult animals, testosterone showed the highest serum levels. In hamsters exposed to a short photoperiod, blood testosterone levels were significantly lower than levels in adult hamsters exposed to a long photoperiod. Exposure of adult hamsters to a short photoperiod produced a marked reduction in serum concentrations of dihydrotestosterone and androstane-3 alpha, 17 beta-diol, which was not accompanied by a decrease in testicular 5 alpha-reductase activity. In the in vitro experiments, active adult testes were less sensitive than inactive adult testes to stimulation of androgen production with hCG, but showed similar sensitivity to the gonads from hamsters aged 36 days. In accordance with circulating androgen concentrations, the principal androgens produced in the in vitro assays from peripubertal and normal adult testes were androstane-3 alpha, 17 beta-diol and testosterone, respectively. Unexpectedly, the main androgen produced from regressed testes under in vitro conditions was androstane-3 alpha, 17 beta-diol. Inactive gonads released more androstane-3 alpha, 17 beta-diol than did normal adult testes and total in vitro androgen production (testosterone + dihydrotestosterone + androstane-3 alpha, 17 beta-diol) from adult testes was not diminished by exposure to a short photoperiod. However, in spite of the significant increase detected in production of androstane-3 alpha, 17 beta-diol in vitro from regressed testes, inactive gonads produced less androstane-3 alpha, 17 beta-diol than did peripubertal testes. In summary, our studies suggest that testicular androgen biosynthetic capacity in adult hamsters exposed to short photoperiod is not reduced and these regressed testes represent an intermediate physiological state between peripubertal and active adult testes. The significant decrease detected in serum androgen concentrations during the involution phase could result from the absence of stimulating pituitary factors, together with a negative regulation of steroidogenesis by different non-steroidal signals originating within and/or outside of the testis.     

Early effects of hCG on human testicular cyclic AMP content, protein kinase activity, in-vitro progesterone conversion and the serum concentrations of testosterone and oestradiol

Ten infertile men underwent testicular biopsy. Cyclic AMP concentration and cAMP-dependent protein kinase activity were determined in biopsies obtained before, and at 3, 10, 20 and 30 min after an intravenous injection of hCG (1500-5000 IU). The in-vitro conversion of progesterone by testicular tissue, and the serum concentrations of testosterone and oestradiol were then studied before and at 30 min after hCG injection. Intravenous injection of hCG induced a rapid increase in cAMP concentration and in the activity of cAMP-dependent protein kinase. The kinetics of this response indicated that cAMP and cAMP-dependent protein kinase mediate hCG effects on the human testis, presumably via effects on the Leydig cells. No stimulatory effect on steroid conversion in vitro or on the serum concentrations of testosterone and oestradiol were seen after 30 min.     

Percutaneous absorption of 5α-dihydrotestosterone in man

The distribution of 5α-dihydrotestosterone to the blood following application of a solution of this androgen to the skin in a hydro-alcoholic gel was studied in order to evaluate the adequacy of the percutaneous route in correcting androgen deficiencies. In 14 adult men, daily percutaneous administration of 5α-dihydrotestosterone (125 mg in 5 g gel) increases, on the average, 4 to 5 times its initial concentration in plasma. On the 14th day of treatment, repeated evaluations of plasma 5α-dihydrotestosterone, between 2 and 21 h after final administration of gel, demonstrated the stability of diurnal 5α-dihydrotestosterone levels and showed the regular distribution of the steroid from a presumably cutaneous reservoir. Plasma 5α-androstane-3α, 17β-diol levels evolve parallel to those of 5α-dihydrotestosterone. Plasma testosterone and luteinizing hormone, on the contrary, decrease considerably. No variation of follicle-stimulating-hormone is observed during treatment. The percutaneous absorption represents an interesting method for administration of a natural androgen in men, particularly because one avoids the deleterious effects of supra-physiological levels in the liver achieved with oral administration.     

Effect of testicular capsulotomy on secretion of testosterone and gonadotrophins in rats

Aim: In order to clarify further the mechanisms underlying the effect of capsulotomy on testicular function, the levels of testosterone, LH and FSH were observed. Methods: Intratesticular testosterone levels and LH, FSH levels in the peripheral blood of normal, sham-operated and capsulotomized rats were detected by RIA. Results: After testicular capsulotomy, there was a progressive reduction in the testosterone level in the testicular venous blood together with a progressive increase in the LH and FSH levels in the peripheral blood from approximately 30 days post-capsulotomy. Morphological changes were observed at 5-10 days after capsulotomy, i.e., far ahead of the hormonal changes.Conclusion: The seminiferous tubular damage after testicular capsulotomy was not caused by the reduction in testosterone, and on the contrary, the hormonal change might be secondary to the morphological alterations. The increase in LH level most likely resulted from a negative feedback influence from the lowered testosterone level, while the increase in FSH secretion may be a feedback signal of the damaged seminiferous tubules. (Asian J Androl 2000 Dec;2:257-261)     

Androgen administration in middle-aged and ageing men: effects of oral testosterone undecanoate on dihydrotestosterone, oestradiol and prostate volume

The gradual reduction of plasma testosterone in middle-aged and older men from mid-life onwards coincides paradoxically with the time when there is progressive growth of the prostate, a highly androgen-dependent organ. The growing interest in androgen therapy for older men makes it essential to understand the effects of exogenous testosterone on the non-diseased prostate, yet few studies are available. The present study examined prostate volume, prostate-specific antigen (PSA) and lower urinary tract symptom (IPSS) score in 207 men, aged 40-83 years, presenting with clinical features of age-related androgen deficiency [sexual and/or urinary dysfunction, elevated lutenizing hormone (LH)] who were treated for 6 months with oral testosterone undecanoate (TU). Men were divided into two groups, group 1 (n=92, plasma testosterone levels > 13 nmol/L) were treated with 80 mg daily; group 2 (n=115, plasma testosterone levels < 13 nmol/L) were treated with given 120 mg daily. Before treatment and after 1, 3 and 6 months of treatment, prostate volume was measured by ultrasound and hormones [testosterone, dihydrotestosterone, oestradiol, LH, follicle-stimulating hormone (FSH)] and PSA were measured. Within 1 month of treatment, the elevated blood LH levels were markedly decreased in all men in group 1, as well as most men in group 2. Group 2 was subdivided into men whose LH levels were suppressed (n=95, group 2a) and those whose LH levels did not suppress (n=20, group 2b). Men in group 1 and 2a had marked decreases in prostate volume, PSA and lower urinary tract symptom (IPSS) scores whereas no significant changes were observed in group 2b. Groups 1 and 2a also had more striking suppression of LH, FSH, dihydrotestosterone and oestradiol whereas group 2b had no significant increases in blood testosterone concentrations. These findings suggest that exogenous testosterone in middle-aged and older men with some clinical features of age-related androgen deficiency can retard or reverse prostate growth and that elevated plasma LH may be a useful index of severity of age-related androgen deficiency.     

The role of a non-androgenic testicular factor in the process of testicular descent in the dog

Previous experiments with orchidectomized foetal and neonatal dogs have shown that the testis can induce outgrowth as well as regression of the gubernaculum testis and consequently, govern both the first and second phases of testicular descent. The aim of this study was to test whether it was possible to prevent the effects of orchidectomy on the gubernacular reaction and on epididymal migration by the administration of testosterone or by auto-transplantation of testicular tissue. In dogs, orchidectomized during foetal life and supplemented with testosterone, gubernacular regression was not completely prevented, and some descent of the remaining epididymis was obvious. However, the descent was less than in normal, intact animals. In dogs orchidectomized neonatally and supplemented with testosterone, the gubernacula showed normal regression and an almost normal descent of the epididymis. In dogs orchidectomized neonatally and supplemented with an auto-transplant of testicular tissue into to the scrotum, normal gubernacular development and normal epididymal descent were observed. We concluded that together with an unidentified non-androgenic testicular factor, testosterone from the testis appears to play a role in the outgrowth phase of the gubernaculum and consequently, in the first phase of testicular descent. In addition, testosterone was found to induce gubernacular regression in the second phase of testicular descent.     

Effect of a single dose of malathion on spermatogenesis in mice

Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acetylcholinesterase(ACE) activity, spermatozoa (epididymal cauda counts and teratozoospermia), testis and plasma testosterone concentration) were evaluated at day 1, 8, 16, 35 and 40 after treatment. Results: The sperm count was decreased significantly 24 h after treatment and teratozoospermia was increased at day 35 and 40. The height of the seminiferous epithelium and the diameter of tubular lumen were decreased at day 8. The percentage of tubular blockade was increased between day 8 and 35. A decrease in testosterone plasma level was observed at day 16 after treatment.Conclusion: Malathion damages male reproduction. The depletion of seminiferous tubules and the increase in teratozoospermia may be a genotoxic damage to the renewing spermatogonia, but the possibility of spermatogenic!spermiogenic disfunction due to a decrease in the plasma testosterone level can not be ruled out. ( Asian J Andro1 2003 Jun; 5:105-107 )     

Effect of an antiestrogen on the testicular response to acute and chronic administration of hCG in normal and hypogonadotropic hypogonadic men: tamoxifen and testicular response to hCG

The effect of the antiestrogen tamoxifen (Tx) on the acute and chronic hCG administration was evaluated in patients with hypogonadotropic hypogonadism (HH) and in normal men. An hCG test (5000 IU hCG) was performed before, after two months of hCG administration (2000 IU hCG three times weekly) and after two months of hCG + Tx (2000 IU hCG three times weekly plus 20 mg/day of tamoxifen). Blood samples were obtained before and following 24 and 72 h of every test to determine T, E, 17OHP and SHBG. T increased only in HH with both treatments (X +/- SEM: Basal: 97.9 +/- 19.7; hCG: 237.7 +/- 43.2; hCG +/- Tx: 204.7 +/- 10.7 ng/100 ml). 17OHP rose with hCG alone, but not with hCG + Tx in both groups. E, SHBG and 17OHP/T ratio did not change after treatments. hCG tests: E increased 24 h following hCG administration in every test. The ratio 17OHP/T rose at 24 h in the first and second test but in the third test it did not change. These results support the role of E in the acute hCG-induced Leydig cell desensitization. However, the association of Tx does not improve T serum levels, suggesting that E might not be the unique factor involved in the mechanisms for testicular desensitization.     

Effects of human chorionic gonadotrophin, oestradiol and estromustine on testicular blood flow in hypophysectomized rats

The effects of human chorionic gonadotrophin (hCG), eostradiol benzoate (E2) and estromustine (Eo) on testicular and prostatic blood flow and plasma levels of testosterone were studied in hypophysectomized rats. Daily injections of 5 IU hCG induced a significant increase in testicular blood flow when measured after 8-9 days treatment. This stimulatory effect was inhibited by concomitant injection of E2 (50 micrograms/day) but not by Eo. In contrast, the stimulatory effect of hCG on plasma levels of testosterone was inhibited by administration of E2 as well as by Eo. This inhibition was correlated with decreased blood flow to the prostate. The present study gives further support to the hypothesis the oestrogens have direct effects on the testis and prostate.     

The effect of clomiphene citrate on sex hormone binding globulin in normospermic and oligozoospermic men

The effect of clomiphene citrate (CC) on sex hormone binding globulin (SHBG) was studied in 10 oligozoospermic patients with varicocele and 6 normospermic men. Plasma SHBG, testosterone (T), oestradiol (E₂), FSH, LH. Prolactin (Prl), thyroxine (T₄) and 17-OH-progesterone (17-OH-P) were determined before and during medication. SHBG concentration rose from 38.1 ± 18.3 to 54.3 ± 16.0 nmol/l ( P < 0.01), while T and E₂ showed significant increases from 31.2 ± 10.8 nmol/***l and 24.6 ± 5.4 pg/ml to 52.0 ± 3.6 and 43.3 ± 14.9, respectively in the oligozoospermic patients, with similar rises noted in the normospermic men. FSH, LH and 17-OH-P were markedly elevated while on CC, but Prl and T₄ remained unchanged. The findings of this study indicated that CC causes an increase of SHBG concentration, which is probably related to the rise of E₂ concentration. This SHBG change, combined with the intrinsic oestrogenic activity of CC might be one of the factors responsible, through a decrease of free T and a T to E₂ imbalance, for the lack of a significant effect on parameters of seminal quality in so treated patients.     

Interaction of hCG with testicular interstitial fluid produces a leucotactic factor

An intratesticular injection of hCG (5 ng) mixed with testicular interstitial fluid (IF) increases vascular permeability in the rat testis. The present results show that the permeability increase induced by this treatment is accompanied by a massive accumulation of polymorphonuclear leucocytes (PMNs) in both the testicular postcapillary venules and the interstitium. Depletion of neutrophils in the circulation by treatment with anti-neutrophil serum significantly inhibited the permeability increase induced by this treatment. An intratesticular injection of PMNs (10(7) cells) or hCG alone had no effect on permeability, but a combination of the two caused a significant increase in permeability. The PMNs were found to secrete a component in vitro which, when injected intratesticularly together with hCG, caused a increase and a simultaneous massive accumulation of PMNs in the postcapillary venules and interstitium. This permeability increase was prevented by the serine protease inhibitor p-aminobenzamidine, suggesting an involvement of the plasminogen activator system in the response. The results suggest that hCG interacts with an IF component to produce leucotactic factors that increase permeability indirectly by attracting PMNs to the tissue, and that the IF component may originate in the PMNs.