Peripheral Testosterone Levels Research Articles

The ageing male

With prolonged life expectancy, men and women can expect to live one-third of their lives with some form of hormone deficiency. The ageing male, in particular, has the added problem of developing urological diseases, such as benign prostatic hyperplasia (BPH), prostate cancer, continence disorders and erectile dysfunction. When discussing age-related problems, it is often difficult to separate and to distinguish between the natural ageing process, ageing amplifiers and an acute or chronic illness, or inter-current diseases. Partial endocrine deficiencies of ageing are associated with a decrease in the peripheral levels of testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEA-S), growth hormone, insulin-like growth factor and melatonin. There is also a concomitant increase in luteinising hormone and follicle stimulating hormone. The concentration of free biologically active testosterone is lowered further by an increase in sex hormone binding globulin (SHBG). Hormonal changes in the ageing male are associated with changes in the body mass index, osteoporosis, sleep and mood disorders. A number of testosterone replacement therapies are available. These therapies should maintain physiological levels not only of serum testosterone, but also of its metabolites, including dihydrotestosterone (DHT) and estradiol. Men on testosterone therapy should be monitored at 3-month intervals during the first year of use and, thereafter, at 1-year intervals if they are stable. The association of testosterone replacement with development of prostate cancer has not been determined.

Assessment of the androgen environment within the human testis: minimally invasive method to obtain intratesticular fluid.

Previous studies of the rat have shown that testosterone concentrations within the interstitial and seminiferous tubularfluids of the testes are significantly higher than normal serum levels, and further, that although intratesticular testosterone concentration can be substantially reduced without an effect on spermatogenesis, the concentration that is minimally required to maintain spermatogenesis is also substantially higher than serum levels. The purpose of the present study was to adapt a minimally invasive technique to sample human intratesticular fluid to enable parallel observations in man. To this end, aspiration methods were first developed for the rat testis and then adapted to the human. The testosterone concentration in fluid obtained by unilateral aspiration of rat testes was approximately 50 ng/mL, similar to the known concentration in seminiferous tubular fluid. These aspiration methods were then adapted to obtain intratesticular fluid from human testes. Studies of 12 fertile human subjects demonstrated that percutaneous testicular aspiration could be performed safely and successfully using a 19-gauge needle. Nine additional human subjects had bilateral testicular aspiration and simultaneous measurement of peripheral blood testosterone levels. Testicular aspirations yielded 8 to 117 microL of fluid from each testicle. The mean concentration of testosterone in aspirates obtained from the 21 patients was 609 +/- 50 ng/mL. Dihydrotestosterone and 3alpha-androstanediol concentrations were quite low, below the limits of detection of our assay. The SHBG/ABP concentration in the aspirates was 8.5 +/- 1.1 nM. These results define testosterone as the major androgenic steroid in the human testis, as in the rat testis, and indicate that the testosterone concentration within the human testis is approximately 200-fold greater than that of SHBG/ABP, and more than 100-fold greater than the concentration of testosterone found in normal human serum.

Cavernous and systemic testosterone levels in different phases of human penile erection

Objectives. To examine changes in testosterone levels in the cavernous and peripheral blood during different phases of erection because, although the determination of systemic testosterone levels has been well established in the diagnostic workup of erectile dysfunction, the exact role of testosterone in adult male sexual function remains unclear. Methods. Blood samples were drawn simultaneously from the corpus cavernosum and the cubital vein of 54 healthy and normally potent volunteers during four different stages of the cavernous erectile tissue (flaccidity, tumescence, rigidity, and detumescence). Penile erections were induced by audiovisual and tactile stimulation, and testosterone levels were determined by radioimmunoassay. Results. The mean testosterone level in the corpus cavernosum plasma during the flaccid state was 2.9 ± 1.2 ng/mL. During tumescence and rigidity, the testosterone levels in the cavernous blood significantly increased, to 4.3 ± 1.3 ng/mL and 4.4 ± 1.4 ng/mL, respectively. During detumescence, the cavernous testosterone levels dropped to 3.5 ± 1.4 ng/mL. The changes in the testosterone levels in the peripheral plasma were less pronounced. A significant increase was also found in the peripheral testosterone levels from flaccidity (4.1 ± 1.1 ng/mL) to tumescence (4.4 ± 1.4 ng/mL). No further increase in testosterone occurred during the phase of rigidity. From rigidity to detumescence, the peripheral testosterone levels dropped to 4.1 ± 1.2 ng/mL. Conclusions. Penile erection was found to be accompanied by a significant increase in cavernous and systemic testosterone plasma levels. The estimated difference between the systemic and cavernous testosterone levels during penile flaccidity, when blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone and the activity of testosterone receptors in the corpus cavernosum smooth musculature.

Ovarian testosterone secretion during perimenopause

Objective: The aim of the study was to investigate ovarian testosterone secretion during the last few years of reproductive life and after menopause. Materials and methods: Ovarian and peripheral venous levels of total testosterone were analyzed in 52 women aged 42–69 years (mean 51) undergoing hysterectomy with adnexal removal for benign indications at the Department of Obstetrics and Gynecology at Tampere University Hospital, Finland. The study population was divided into pre- ( n=19), peri- ( n=18) and postmenopausal ( n=15) women in addition to the classical division according to menstrual cycle. Corresponding serum estradiol, progesterone and gonadotropin levels were measured, and the degree of ovarian stromal hyperplasia was analyzed. Results: The levels of all steroid hormones were higher in the ovarian vein than in the periphery. A significant positive correlation was found between age and ovarian vein testosterone levels ( r=0.3, P=0.01). In premenopausal women, it was 1.5 nmol/l (median; range 0.78–6.0), in perimenopausal women 2.2 nmol/l (range 0.9–13.6), and 2.5 nmol/l (range 0.6–26.6) in postmenopause, respectively. Peripheral testosterone level did not increase with age. Ovarian stromal hyperplasia was significantly associated with increased testosterone secretion ( P=0.009). Conclusion: The ovary seems to increase the secretion of testosterone into circulation during the menopausal transition period, as the highest levels were measured in postmenopausal women. High testosterone levels in the ovarian vein, however, were not reflected in the peripheral venous blood.

Taxonomic status and sex identification from single follicle hairs in endangered Pyrenean Ibex (Capra pyrenaica pyrenaica)

Seasonal variations in the horn development and testicular activity of the Spanish ibex (Capra pyrenaica hispanica) (n = 6) and European mouflon (Ovis orientalis musimon) (n = 5) were monitored to determine the role of increasing testosterone concentration on the arrest of horn growth during the rutting season. Marked seasonal variations in the rate of horn growth (P < 0.01) and testicular activity (P < 0.001) were seen in both species, although the magnitude and timing of these changes were different (P < 0.01). Horn growth rate was inversely correlated to seasonal levels in testosterone plasma concentration in both species (ibex: R = −0.45, P < 0.01; mouflon R = −0.51, P < 0.01). In the mouflon, the increase in plasma testosterone concentration recorded in September (P < 0.05 compared with the lowest concentration) coincided with a significant reduction in horn growth (P < 0.05). In the ibex, the increase in plasma testosterone concentration in October (P < 0.05 compared with the lowest concentration) was associated with a significant arrest of horn growth in November (P < 0.05). These results appear to support the hypothesis that high peripheral plasma levels of testosterone are linked with the seasonal arrest of horn growth during the rutting period.

Comparison of the effects of chlormadinone acetate‐pellet implantation and orchidectomy on benign prostatic hypertrophy in the dog

Five beagles out of 11 dogs aged 7-10 years with benign prostatic hypertrophy (BPH) were implanted subcutaneously with pellets of the synthetic anti-androgen chlormadinone acetate (CMA) at a dose of 10 mg/kg bodyweight. The remaining six dogs (one beagle and five mongrel dogs) underwent bilateral orchidectomy. Changes in prostatic volume, histological findings in the prostate and the testis, and peripheral plasma levels of LH, testosterone and oestradiol-17 beta (E2) were assessed up until 24 and 4 weeks after CMA-implantation and orchidectomy, respectively. Measurements of the size of the prostate and biopsies of the prostate were performed by laparotomy. Mean prostatic volume had decreased to 71% and 41%, respectively, of its pretreatment volume, by 4 weeks after CMA-implantation and orchidectomy, and was 49% and 47%, respectively, of pretreatment volume at 12 and 24 weeks after CMA-implantation. The clinical signs of BPH, e.g. haematuria, resolved within 2 weeks after either treatment. When the prostate was examined histologically 4 weeks after either treatment, hardly any evidence of active secretion (e.g. glandular epithelium projecting markedly into the lumen), was observed in CMA-implanted dogs, alveolar diameter and height of the glandular epithelium had decreased markedly and the glandular lumen had become very small in the orchidectomized dogs. By 12 weeks after CMA-implantation, degenerative and atrophic glands were observed in the prostate nearly the same as at 4 weeks after orchidectomy. In the testis the number of germ cells in the seminiferous tubules decreased markedly after CMA-implantation. The mean level of plasma LH at 4 weeks after orchidectomy had increased to 14.9 ng/ml, twice the value before operation. The mean levels of plasma testosterone and E2 at 4 weeks after CMA-implantation had decreased to 0.7 ng/ml and 9 pg/ml from 1.5 ng/ml and 15 pg/ml, the values before treatment, respectively. CMA-implantation resulted in poor semen quality. The results indicate that CMA-implantation at a dose of 10 mg/kg results in the same prostate-shrinking effect as orchidectomy.

A non‐human primate study (baboon; Papio hamadryas) to determine if a long‐acting progestogen, levonorgestrel butanoate, combined with a long‐acting androgen, testosterone buciclate, can suppress spermatogenesis: II. Efficacy study

Two combined injections of levonorgestrel butanoate (4 mg/kg) and testosterone buciclate (8 mg/kg) at 3-month intervals to adult male baboons initiated a decrease in sperm concentration from baseline values of 490x10(6)/ml to minimum values of 17x10(6/ml. This suppression was sustained until week 32, during which time between one and three azoospermic samples were collected from each of four out of five treated baboons in the period 10-24 weeks. Circulating plasma levels of LH and testosterone decreased to approximately 20-75% of baseline values. Plasma levels of cortisol declined to significantly reduced levels at weeks 22 and 36-44. All values returned to the baseline range by week 48. The combined administration of progestogen and androgen induced a more marked and sustained suppression to severe oligozoospermia or azoospermia than did the equivalent dose of progestogen alone (Goncharov et al., 1995). Although the dose of testosterone buciclate used did not maintain peripheral levels of testosterone in the normal range, it did not restimulate spermatogenesis. It was concluded that a combination drug regimen based on the novel long-acting levonorgestrel and testosterone esters could provide a contraceptive option for men.

Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism.

Administration of the goitrogen, 6-propyl-2-thiouracil (PTU), to suckling rat pups from birth through day 24 postpartum as a 0.1% solution in the mother's drinking water increases adult testis size and sperm production by about 80% and 140%, respectively, without affecting peripheral testosterone levels. The objectives of this study were to determine whether adult Leydig cell numbers were altered in PTU-treated rats and whether the steroidogenic function of these cells was normal. The number of Leydig cells per testis at 180 days increased by 69% in PTU-treated compared to control rats, whereas the average Leydig cell volume declined by about 20%. Steroidogenic function assessed in isolated adult Leydig cells decreased after neonatal PTU treatment. LH-stimulated testosterone production was reduced by 55% in Leydig cells from treated rats, commensurate with a 50% decline in the number of hCG-binding sites in these cells. The difference in steroidogenic potential was even more striking after incubations with saturating concentrations of steroid substrate, 22(R)-hydroxycholesterol; Leydig cells from treated males produced 73% less testosterone than controls. Therefore, this decrease in testosterone production may be partially due to a reduction in the numbers of LH receptors, but also reflects the impaired steroidogenic potential of these cells. These results clearly show that the dramatic increase in adult Leydig cell number after neonatal PTU treatment is counterbalanced by a permanent decline in Leydig cell steroidogenic function, producing no net change in peripheral testosterone levels.

Leydig cells increase their numbers but decline in steroidogenic function in the adult rat after neonatal hypothyroidism

Administration of the goitrogen, 6-propyl-2-thiouracil (PTU), to suckling rat pups from birth through day 24 postpartum as a 0.1% solution in the mother's drinking water increases adult testis size and sperm production by about 80% and 140%, respectively, without affecting peripheral testosterone levels. The objectives of this study were to determine whether adult Leydig cell numbers were altered in PTU-treated rats and whether the steroidogenic function of these cells was normal. The number of Leydig cells per testis at 180 days increased by 69% in PTU-treated compared to control rats, whereas the average Leydig cell volume declined by about 20%. Steroidogenic function assessed in isolated adult Leydig cells decreased after neonatal PTU treatment. LH-stimulated testosterone production was reduced by 55% in Leydig cells from treated rats, commensurate with a 50% decline in the number of hCG-binding sites in these cells. The difference in steroidogenic potential was even more striking after incubations with saturating concentrations of steroid substrate, 22(R)-hydroxycholesterol; Leydig cells from treated males produced 73% less testosterone than controls. Therefore, this decrease in testosterone production may be partially due to a reduction in the numbers of LH receptors, but also reflects the impaired steroidogenic potential of these cells. These results clearly show that the dramatic increase in adult Leydig cell number after neonatal PTU treatment is counterbalanced by a permanent decline in Leydig cell steroidogenic function, producing no net change in peripheral testosterone levels.

Effects of LHRH‐analogue treatment of spermatogenic dysfunction in the dog

Three male dogs, aged 2-4 years, which exhibited a high percentage of sperm with abnormal tails in their semen and low levels of peripheral plasma LH and testosterone were given two injections of 400 micrograms an LHRH analogue (LHRH-A) 3 h apart. The semen quality of all three dogs and the peripheral plasma levels of LH and testosterone were examined in two of the dogs. Plasma levels of LH and testosterone in both dogs peaked at 30 and 90 min respectively, after the injection of LHRH-A. The semen quality of all three dogs had improved temporarily 20 days after the injection. To be specific, although the mean percentage of sperm with abnormal tails in the three dogs was 19, 26 and 32% respectively before injection of LHRH-A, these values had decreased to 10, 16 and 13%, respectively, 20-40 days later. Thereafter, however, the percentage sperm abnormalities increased again. The testes and epididymides of two of the dogs were examined histologically at the end of 90 days. Sloughed germ cells were observed in the seminiferous tubules of the testes, and pyknotic epithelial cells were noted in some of the epididymal ducts. The other dog, which had a history of three unsuccessful matings was treated again with LHRH-A and mated with three bitches 30, 75, and 110 days later, respectively. Only the bitch mated with this dog 30 days after a second series of injections conceived. It is assumed that the semen quality of the three dogs improved because of a temporary rise in plasma LH and testosterone levels after the injection of LHRH-A. It is concluded that the fertility of dogs with a high percentage of sperm with abnormal tails can be improved approximately 30 days after treatment with an LHRH-A.

Inhibin, gonadotrophins and sex steroids in dogs with Sertoli cell tumours

Inhibin bioactivity and mRNA for inhibin subunits were measured in four dog Sertoli cell tumours and in the testes of five normal control dogs. The tumours contained increased levels of inhibin (P less than 0.05) and mRNA for the alpha and beta B subunits when compared with controls, whereas the mRNA for the beta A subunit was not detected in tumours or control testes. The inhibin bioactivity was associated with a 32 kDa molecule in both Sertoli cell tumours and normal dog testes; no higher molecular weight forms were found after sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Peripheral levels of immunoassayable inhibin in dogs with Sertoli cell tumours were higher than those in the controls (P = 0.01), indicating that it might be possible to use this parameter as a marker for Sertoli cell tumours. Other testicular tumours, however, might also secrete immunoactive inhibin. The increased inhibin concentrations are likely to be the cause of the suppressed peripheral levels of FSH (P less than 0.02). However, peripheral levels of LH (P less than 0.02) and testosterone (P less than 0.01) were also suppressed in the dogs with Sertoli cell tumours, whereas the concentrations of oestradiol in the peripheral plasma of both groups did not differ. Finally, i.v. injection of the LHRH agonist buserelin caused a significant increase in LH and testosterone in the control dogs, but not in the dogs with Sertoli cell tumours. It was concluded that secretory products from the Sertoli cell tumours suppressed pituitary gonadotrophin secretion. It is unlikely that testosterone or oestradiol play a role in this respect. FSH may be suppressed by the high levels of inhibin in tumour-bearing dogs, but it remains unclear whether inhibin or another Sertoli cell product is responsible for the unresponsiveness of the pituitary gland to LHRH and the suppression of LH.

Peripheral plasma levels of LH, testosterone, and estradiol-17.BETA. before and after orchiopexy in unilaterally cryptorchid dogs.

Peripheral plasma levels of LH, testosterone, and estradiol-17.BETA. before and after orchiopexy in unilaterally cryptorchid dogs.

Synthesis and aromatization of 19-norandrogens in the stallion testis

The results of the measurement of 19-nortestosterone in the testiscular artery and vein of the stallion, the very low levels of this steroid in the peripheral blood of geldings and the similar patterns of increase in the peripheral levels of 19-nortestosterone and testosterone after hCG stimulation, show that 19-nortestosterone, like testosterone, is essentially synthesized in the testis. This testicular origin was confirmed by the ability of testicular tissue to synthesize 19-norandrogens from [4- 14C]androgens in vitro. 19-Nortestosterone was 50% conjugated in the peripheral blood and almost entirely conjugated after biosynthesis in vitro. The sequence of appearance of steroids in the peripheral blood after a single injection of 10,000 IU hCG suggests that, in the equine testis, 19-norandrogens are produced by a specific C10–19 desmolase (estrene synthetase), stimulable by hCG. 19-Nortestosterone was aromatized into estradiol-17β by stallion testicular microsomes. The affinity of the aromatase for 19-nortestosterone was very low compared to that for testosterone. At low and presumably physiological levels, and at a high testosterone/19-nortestosterone ratio, testosterone did not inhibit 19-nortestosterone aromatization by more than 53%. Thus, 19-nortestosterone may be aromatized in vivo in the testis in spite of the endogenous concentrations of androgens. However, the low velocity of 19-nortestosterone aromatization by testicular microsomes at roughly physiological concentrations suggests that 19-norandrogen aromatization may only participate slightly in the testicular estrogen production. These results suggest that in the equine testis, two aromatizing enzyme systems may exist: one which aromatizes both androgens and 19-norandrogens, and a minority system more specific for 19-norandrogens.

Preoperative Localization of Androgen-Secreting Tumors

Abstract A series of 10 patients with benign androgen-secreting neoplasms is presented. Nine tumors were ovarian, and one adrenal. In an attempt to correctly diagnose the presence of tumor and to accurately localize the lesion to a specific gland, steroid hormones in peripheral, ovarian, and adrenal vein serum were analyzed by radioimmunoassay. Little correlation was made in this series with those levels of testosterone (>2 ng/ml) or dehydroepiandrosterone sulfate (>7000 ng/ml) that have been widely used to predict the presence of such tumors. Peripheral testosterone levels were less than 2 ng/ml in 50% of our patients, and the dehydroepiandrosterone sulfate level was greater than 7000, ng/ml in only a single patient with an ovarian lipoid cell tumor. Pelvic ultrasonography was found to be of limited value in evaluating nonpalpable tumor because of the small size ( 3 ) of the majority of these neoplasms. The use of selective retrograde venous catheterization to demonstrate significant effluent-peripheral vein androgen gradients served to accurately localize androgen-secreting tumors in all six patients in which it was used. Our data emphasize the potential pitfalls that exist in the preoperative evaluation of patients with these fascinating neoplasms and the importance of a high degree of suspicion on the part of the physician caring for these women.

123 GYNECOMASTIA IN THE PEUTZ-ZEGHERS SYNDROME IS CAUSED BY TESTICULRA TUMOR AROMATASE PRODUCTION

Gynecomastia was present in a 4 yr old boy without pubic hair or phallic enlargement but with growth acceleration, early pubertal testicular enlargement and a bone age of 8 yr. The patient and his father have Peutz-Jeghers syndrome. Testicular ultrasound showed diffuse disruption of the gonadal parenchyma in the patient but not in his father. Peripheral levels of testosterone (T), estradiol (E2) and gonadotropins were prepubertal. Testicular vein blood samples revealed T levels of 680 and 690 pg/ml, 1/1000 the concentrations reported in adult men; in contrast, E2 measurements of 1270 and 1150 pg/ml were similar to adult male levels, indicating increased T to E2 synthesis. Testicular biopsies showed bilateral, multi-focal sex cord tumors with annular tubules. Aromatase activity assessed in tumor homogenates revealed the production of 4 22 pmol estrone/gm wet weight tissue/hr, two-thirds of the enzyme amounts found in human placenta. Aromatase was also detected by peroxidase-antiperoxidase immunocytochemistry using a specific monoclonal antibody and was localized within the cytoplasm of abnormal appearing Sertoli cells. In conclusion, increased tumor expression of a single enzyme resulted in excess steroid production (E2) and symptoms thereof, without evidence of elevated substrate (T). Testicular aromatasomas are a unique cause of prepubertal gynecomastia.

Preoperative localization of androgen-secreting tumors: Clinical, endocrinologic, and radiologic evaluation of ten patients

A series of 10 patients with benign androgen-secreting neoplasms is presented. Nine tumors were ovarian, and one adrenal. In an attempt to correctly diagnose the presence of tumor and to accurately localize the lesion to a specific gland, steroid hormones in peripheral, ovarian, and adrenal vein serum were analyzed by radioimmunoassay. Little correlation was made in this series with those levels of testosterone (>2 ng/ml) or dehydroepiandrosterone sulfate (>7000 ng/ml) that have been widely used to predict the presence of such tumors. Peripheral testosterone levels were less than 2 ng/ml in 50% of our patients, and the dehydroepiandrosterone sulfate level was greater than 7000, ng/ml in only a single patient with an ovarian lipoid cell tumor. Pelvic ultrasonography was found to be of limited value in evaluating nonpalpable tumor because of the small size (<2 cm3) of the majority of these neoplasms. The use of selective retrograde venous catheterization to demonstrate significant effluent-peripheral vein androgen gradients served to accurately localize androgen-secreting tumors in all six patients in which it was used. Our data emphasize the potential pitfalls that exist in the preoperative evaluation of patients with these fascinating neoplasms and the importance of a high degree of suspicion on the part of the physician caring for these women.

Stimulation of interstitial cell growth after selective destruction of foetal Leydig cells in the testis of postnatal rats.

Five-day-old male rats received a single treatment of ethane dimethanesulphonate (EDS), and the response of the testis on days 6-10 and 21 was examined by light microscopy and morphometry, supplemented by measurement of peripheral testosterone levels. One day after treatment, foetal Leydig cells degenerated, showing fragmentation, condensation and nuclear pyknosis. Macrophages phagocytosed the foetal leydig cells resulting in their disappearance by day 7. Destruction of foetal Leydig cells was followed by an arrest of testicular growth in comparison to testes of intact age-matched control rats. In testes of EDS-treated rats, gonocytes and spermatogonia also degenerated, forming pyknotic bodies within the seminiferous cords. In contrast, interstitial fibroblasts and mesenchymal cells showed proliferative activity, which on days 4 and 5 after treatment resulted in peritubular hyperplasia surrounding each seminiferous cord. Thereafter, on day 21 after EDS administration, the previously depressed serum testosterone levels became markedly elevated coincident with the development of many immature-type Leydig cells, of which the total volume per testis was similar to that of Leydig cells in control testes, despite a four- to five-fold difference in testicular volumes. The results indicate that, although EDS destroys the foetal Leydig cells and impairs spermatogenesis, the interstitial tissue exhibits increased cell growth. The latter probably occurs in response to altered gonadotrophic stimulation and/or disturbances in the interaction between the seminiferous cords and the interstitial tissue.

Response to human chorionic gonadotropin in patients with ovarian tumors.

The results of hCG stimulation on peripheral levels of androstenedione (A), testosterone (T) and estrone (E1) were examined in 14 patients with ovarian tumors and in 9 tumor-free subjects, after the menopause. Following hCG injection, 9 postmenopausal patients with ovarian tumors showed a significant rise in A peripheral levels. The responsive subjects generally had significant increases in A baseline levels, too. The remaining 5 subjects with advanced or poorly differentiated ovarian cancer with no stroma were not responsive to hCG. Moreover, in the tumor group, 7 subjects had increased baseline T and/or E1 and in 3 of them an increase of these steroids was observed following hCG. In the absence of ovarian tumor, no subject in the control group was responsive to hCG administration. The results of the present investigation seem to confirm the in vivo responsiveness to hCG of ovarian tumors.

Age-dependence of the rat Leydig cell and Sertoli cell function.

The first part of this study compares peripheral testosterone levels with intratesticular levels of the cytochromes P-450 of two key enzymes of androgen biosynthesis, i.e. mitochondrial cholesterol monooxygenase (P-450(cscc)) and microsomal steroid-17 alpha-monooxygenase (P-450(C17 alpha)) during puberty and early adulthood of male Wistar rats. From 4 to 10 weeks of age, the testosterone level increases 8.7-fold, the P-450(C17 alpha) level 8.3-fold, but the P-450(cscc) level 24.5-fold as an indication of specific induction of this protein. From 13 to 50 weeks of age, the testosterone level remains constant, the P-450(cscc) level increases continuously by a factor of 1.4, but 62% of the P-450(C17 alpha) content are lost. This discrepancy is explained by a divergent regulation of the cytochromes P-450 of the two steroid monooxygenases: a persisting induction of P-450(cscc) and a concurrent down-regulation of P-450(C17 alpha) that may be a consequence of the high rate of Leydig cell steroid hydroxylation after puberty. Overlapping of both processes may (probably besides other developmental factors) result in a constant testosterone concentration in blood. The second part of the study compares testicular and epididymal levels of androgen-binding protein (ABP) with the peripheral testosterone level. The peripubertal increase in testicular ABP content is shown to be related only to the increase in testicular mass, whereas a specific accumulation of ABP occurs in the epididymis from 4 to 13 weeks of age. This pattern indicates an increasing secretory activity of the Sertoli cells that remains high during adulthood up to the 50th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of natural progesterone treatment during pregnancy on fetal testosterone and sexual behavior of the male offspring in the mouse.

The effect of maternal exposure to progesterone upon the fetal pituitary-gonadal axis and the sexual behavior of the male offspring of mice were studied. Daily injection of progesterone from days 14 to 16 of pregnancy reduced testosterone production in the fetus but caused a significant increase in circulating LH levels. Progesterone-exposed males showed no alteration in anogenital distance or in body weight at any time from birth to adulthood. At 80-90 days of age males from control and progesterone-exposed groups did not differ from each other in testis and seminal vesicle weights. However, in the latter group, there was a marked reduction in the percentage of males that displayed mount, intromission and ejaculation patterns. These findings indicate that in utero exposure to pharmacological doses of progesterone that do not cause abnormalities of male internal and external genitalia may interfere with masculine behavior in adulthood. This alteration could partially be due to diminished peripheral testosterone levels during the prenatal period.