Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “testosterone secretion”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed1999

Seasonal changes in the negative feedback regulation of the secretion of the gonadotrophins by testosterone and inhibin in rams.

Three experiments were conducted with castrated Romney Marsh rams (wethers) to investigate the ability of testosterone and inhibin to suppress the secretion of LH and FSH during the breeding and the non-breeding seasons. In Experiment 1, wethers (n=5/group) were treated every 12 h for 7 days with oil or 16 mg testosterone propionate (i.m.) and were then given two i.v. injections either of vehicle or of 0.64 microg/kg human recombinant inhibin A (hr-inhibin) 6 h apart. Blood samples were collected for 4 h before inhibin or vehicle treatment and for 6 h afterwards for the assay of LH and FSH. In Experiments 2 and 3 wethers underwent hypothalamo-pituitary disconnection (HPD) and were given 125 ng GnRH i.v. every 2 h. In Experiment 2, HPD wethers (n=3/group) were injected (i.m.) every 12 h with oil or testosterone and blood samples were collected over 9 h before treatment and 7 days after treatment. In Experiment 3, HPD (n=5/group) wethers were treated with vehicle or hr-inhibin, as in Experiment 1, after treatment with oil, or 4, 8 or 16 mg testosterone twice daily for 7 days. Blood samples were collected over 4 h before treatment with vehicle or hr-inhibin and for 6 h afterwards. Treatment of wethers with testosterone (Experiment 1) resulted in a significant decrease in the plasma concentrations of LH and number of LH pulses per hour but the magnitude of these reductions did not differ between seasons. Testosterone treatment had no effect on LH secretion in GnRH-pulsed HPD wethers in either season and treatment with hr-inhibin did not affect LH secretion in wethers or HPD wethers in any instance. Plasma concentrations of FSH were significantly (P<0.05) reduced following treatment with testosterone alone during the breeding season but not during the non-breeding season. FSH levels were reduced to a greater extent by treatment with hr-inhibin but this effect was not influenced by season. During the non-breeding season, the effect of hr-inhibin to suppress FSH secretion was enhanced in the presence of testosterone. These experiments demonstrate that the negative feedback actions of testosterone on the secretion of LH in this breed of rams occurs at the hypothalamic level and is not influenced by season. In contrast, both testosterone and inhibin act on the pituitary gland to suppress the secretion of FSH and these responses are affected by season. Testosterone and inhibin synergize at the pituitary to regulate FSH secretion during the non-breeding season but not during the breeding season.

Analysis of Variance↗
PubMed2006

Comparative response of rams and bulls to long-term treatment with gonadotropin-releasing hormone analogs.

The objective was to compare the relative response between rams and bulls in characteristics of LH, FSH and testosterone (T) secretion, during and after long-term treatment with GnRH analogs. Animals were treated with GnRH agonist, GnRH antagonist, or vehicle (Control) for 28 days. Serial blood samples were collected on day 21 of treatment, and at several intervals after treatment. Injections of natural sequence GnRH were used to evaluate the capacity of the pituitary to release gonadotropins during and after treatment. Treatment with GnRH agonist increased basal LH and T concentrations in both rams and bulls, with a greater relative increase in bulls. Endogenous LH pulses and LH release after administration of GnRH were suppressed during treatment with GnRH agonist. Treatment with GnRH antagonist decreased mean hormone concentrations, LH and T pulse frequency, and the release of LH and T after exogenous GnRH, with greater relative effects in bulls. Rams previously treated with antagonist had a greater release of LH after administration of GnRH compared with control rams, while rams previously treated with agonist showed a reduced LH response. Bulls previously treated with agonist had reduced FSH concentrations and LH pulse amplitudes compared with control bulls while bulls previously treated with antagonist had greater T concentrations and pulse frequency. The present study was the first direct comparison between domestic species of the response in males to treatment with GnRH analogs. The findings demonstrated that differences do occur between rams and bulls in LH, FSH and testosterone secretion during and after treatment. Also, the consequences of treatment with either GnRH analog can persist for a considerable time after discontinuation of treatment.

Animals↗
PubMed2000

Valproate-induced alterations in testosterone, estradiol and progesterone secretion from porcine follicular cells isolated from small- and medium-sized ovarian follicles.

The aim of the present study was to investigate whether long-term exposure to valproate (VPA) alters follicular steroidogenesis and whether or not this effect is dependent on the degree of follicular development. Small- and medium-sized follicles were obtained from pig ovaries collected, respectively, at days 8-10 and 14-16 of oestrus cycle. Theca interna and granulosa cells were isolated from follicles and placed in the same well in the ratio 1 : 3 with or without the VPA in doses of 100, 300 and 500 micro g ml(-1). The culture medium was changed after 2, 4, 6 and 8 days. In both types of follicles, VPA caused a significant and dose-dependent reduction in both testosterone and estradiol secretion from follicular cells. In small-sized follicles, the testosterone to oestrogen ratio increased at all doses used and after all lengths of time in culture. In medium-sized follicles, a significant increase in the testosterone to oestrogen ratio was only observed at the highest dose level. All doses of VPA caused a marked inhibition of progesterone secretion after 48 hours while during long-term VPA exposure progesterone gradually increased demonstrating luteinization of cells. In conclusion, the present study demonstrates a direct effect of VPA on steroidogenesis. The effect seems to differ to some extent depending on the follicular stage of development. The elevated ratio of testosterone to estradiol suggests that VPA inhibits the conversion of testosterone to estradiol.

Animals↗
PubMed1989

Effects of long-term testosterone administration on gonadotropin secretion in agonadal female to male transsexuals compared with hypogonadal and normal women.

We investigated the effects of long term testosterone (T) administration on pulsatile gonadotropin secretion in agonadal women and the effects of estradiol (E2) on gonadotropin secretion in eugonadal women in the follicular phase of the menstrual cycle. We studied 4 groups: A) 28 eugonadal women in the early follicular phase of the menstrual cycle, B) 11 hypogonadal women, C) 13 agonadal female to male (f-t-m) transsexuals treated for at least 3 months with 120-160 mg T undecanoate (TU)/day, orally, and D) 5 agonadal f-to-m transsexuals treated for at least 6 months with 250 mg of a mixture of testosterone esters, im (im T-esters), every 2 weeks. The eugonadal women in the early follicular phase had a mean serum E2 level of 193 +/- 94 (+/- SD) pmol/L, significantly higher (P less than 0.01) than that in the hypogonadal women (60 +/- 24 pmol/L), whereas there was no difference in the mean serum T levels (1.8 +/- 0.7 vs. 2.3 +/- 1.5 nmol/L). the higher serum E2 level in the eugonadal women was associated with a significantly lower mean serum LH level (6.9 +/- 2.6 vs. 44.6 +/- 17.6 U/L; P less than 0.01) and LH pulse amplitude (2.8 +/- 1.0 vs. 12.6 +/- 4.8 U/L; P less than 0.01), whereas the mean nadir LH interval did not differ between the two groups (75 +/- 29 vs. 81 +/- 49 min). The mean serum T level in the agonadal f-to-m transsexuals treated with oral TU was significantly higher (P less than 0.01) than that in the hypogonadal women (9.7 +/- 4.7 vs. 2.3 +/- 1.5 nmol/L). In spite of this elevated T level there was no difference in the mean serum LH level (38.4 +/- 14.7 vs. 44.6 +/- 17.6 U/L), LH pulse amplitude (14.3 +/- 5.7 vs. 12.6 +/- 4.8 U/L), or nadir LH interval (72 +/- 27 vs. 81 +/- 49 min) in these groups. Also, the mean serum E2 (64 +/- 16 vs. 60 +/- 24 pmol/L and FSH levels (62 +/- 17 vs. 64 +/- 28 U/L) did not differ between these groups. Treatment of the agonadal f-to-m transsexuals with im T-esters resulted in mean serum T and E2 levels of 34.4 +/- 27.0 nmol/L and 121 +/- 54 pmol/L, respectively, both significantly higher (P less than 0.01) than those in groups B and C.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Effect of testosterone on growth hormone secretion in female rats during a continuous infusion of growth hormone releasing factor.

The effect of testosterone on growth hormone (GH) secretory pattern during a 6-hour continuous infusion of human GH-releasing factor (GRF) (1-44) NH2 was observed in unrestrained adult female Wistar rats. Rats had been ovariectomized or sham operated 6 weeks previously. Three weeks after the ovariectomy, the rats received sesame oil or testosterone propionate at a dose of 1 or 2 mg s.c. daily for 21 days. All rats were provided with two indwelling cannulae: one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for vehicle or GRF infusion. Vehicle or GRF was administered by an infusion pump at a dose of 50 ng/kg/min for 6 h. Serial blood specimens were obtained every 20 min. Sham-operated adult female Wistar rats exhibited a high-frequency, low-amplitude pulsatile GH secretion during a 6-hour vehicle infusion. When they received a 6-hour continuous infusion of GRF, the amplitudes of GH pulses and baseline GH values were markedly augmented, but the pulse frequency remained unaltered. The GH secretory pattern during a 6-hour vehicle infusion among ovariectomized rats was similar to that of sham-operated female rats, whereas the magnitude of elevation of GH pulse and baseline level in ovariectomized rats were significantly lower than in sham-operated rats. The ovariectomized female rats that had received 2 mg testosterone for 21 days showed a low-frequency, regularly timed, high-amplitude pulsatile GH secretion, and GH values during the intervening period were low. This GH secretory pattern was indistinguishable from that in adult male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

The relationship between the rat of testosterone infusion and gonadotropin secretion.

Prepubertal and young adult male rats were castrated and continuous intravenous infusions of testosterone were administered for 2-3 days. Blood samples were obtained at various intervals and serum concentrations of FSH and LH were determined. In 43-day-old males a dose of approximately 57 mug/day was required to suppress serum LH to levels observed in intact controls, and FSH was also suppressed at this dose. Within one day after termination of infusions serum LH and FSH concentration had returned to (or exceeded) the levels observed in castrates infused with vehicle only. This was true even after a very large dose of testosterone had been administered (918 mug/day). In 59-day-old males serum LH was suppressed somewhat by 40 mug testosterone/day and further by 200 mug/day. FSH did not appear to be suppressed as readily in these rats as compared to the younger animals. Further experiments in which castrated rats were injected with testosterone or testosterone propionate revealed marked differences in the magnitude and time course of the action of these compounds upon LH release. It is suggested that the rate of metabolism of these steroids is important in limiting their effects, especially when administered by single daily injections. Furthermore, it appears that "recovery" of the hypothalamic-pituitary system from exposure to high concentrations of testosterone is rapid following clearance of the steroid from the blood.

Age Factors↗
PubMedDate not supplied

The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol.

In men, administration of exogenous testosterone (T) exerts direct negative feedback effects at the pituitary as well as at the hypothalamic level. This study was undertaken to determine whether T itself causes the inhibitory effects on the pituitary, or whether conversion to estradiol (E2) or dihydrotestosterone (DHT) is required. We assessed the biological activity of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as immunoactivity. Blood samples were drawn before, during, and after a continuous, 72-hour i.v. infusion of T (15 mg/day), E2 (90 micrograms/day), or DHT (500 micrograms/day). Each of these doses is twice the daily production rate of the steroid. Each man received each of the three steroid infusions. We studied four men, ages 23-35, with idiopathic hypothalamic hypogonadism (IHH), who were treated with pulsatile gonadotropin releasing hormone (GnRH) until their gonadotropins reached the normal range. Serum levels of T, E2, DHT, and levels of immunologically active and biologically active LH and FSH were measured. We found that administration of each steroid increased serum levels of the infused steroid to the upper physiologic range. Administration of T or E2 resulted in decreased mean levels of biologically and immunologically active LH and FSH; administration of DHT did not alter gonadotropin secretion. These data suggest that some of the direct effect of T at the pituitary level in men is mediated by E2, whereas peripherally formed DHT may not play an important role in this process.

Adult↗
PubMed1989

Steroid biosynthesis in the Sertoli-Leydig cell tumor: effects of insulin and luteinizing hormone.

In vitro steroid production by a virilizing Sertoli-Leydig cell tumor of the ovary was studied. For comparison, stromal tissue from the opposite normal ovary was also incubated under similar conditions. The tumor fragments secreted significantly more testosterone (527 +/- 168 versus 48 +/- 29 pg/mg tissue, p less than 0.001), androstenedione (1188 +/- 400 versus 40 +/- 10 pg/mg tissue, p less than 0.001), and dehydroepiandrosterone (419 +/- 132 versus 73 +/- 25 pg/mg tissue, p less than 0.004) than that of normal ovarian stroma. Measurement of steroids in the ovarian venous serum draining the tumor indicated a peripheral ovarian gradient for both delta 4 and delta 5 steroids. Incubation of tumor fragments with luteinizing hormone alone resulted in a significant increase in the secretion of androstenedione and dehydroepiandrosterone (p less than 0.05). Addition of insulin to luteinizing hormone resulted in significantly greater release of androstenedione than that of treatment with luteinizing hormone alone (p less than 0.04). Addition of insulin had no effect on the release of dehydroepiandrosterone. Luteinizing hormone and insulin, either alone or in combination, failed to produce any change in the secretion of testosterone. We conclude that (1) increased testosterone secretion by Sertoli-Leydig cell tumor resulted from increased availability of precursors from both delta 4 and delta 5 pathways; (2) the tumor was responsive to luteinizing hormone with an increase in the secretion of androstenedione and dehydroepiandrosterone; (3) insulin acts synergistically with luteinizing hormone to increase secretion of androstenedione; (4) the tumor has specific binding sites for insulin; and (5) the increased levels of insulin and luteinizing hormone in polycystic ovarian disease may play a role in the pathogenesis of Sertoli-Leydig cell tumor.

Adult↗
PubMed1979

Effects of season on the secretion of LH and testosterone in intact and castrated red deer stags (Cervus elaphus).

At 2--4 monthly intervals during the year blood samples were collected every 15 min for 6 h from 2 intact and 3 castrated red deer stags to study the relationship between season and the secretion of LH and testosterone. In the intact stags plasma LH and testosterone concentrations changed during the year; the LH levels were maximal in August during the phase of testicular redevelopment, while the testosterone levels were maximal from September to November coinciding with the time of peak testicular activity and the mating season. The castrated stags had higher plasma levels of LH than the intact stags at all times of the year, and there was no clear seasonal cycle in LH levels in these animals.

Animals↗
PubMed1988

The effect of testosterone therapy on spontaneous growth hormone secretion in boys with constitutional delay.

Testosterone treatment is known to improve growth hormone (GH) secretion in boys with constitutional delay (CD). To determine whether spontaneous GH secretion is normal after treatment, we assessed GH secretion before and after a four- to five-month course of testosterone enanthate in eight adolescents with CD. Before testosterone therapy, the mean (+/- 1 SD) 24-hour integrated concentration of GH (IC-GH) by constant blood withdrawal technique was 1.7 +/- 1.0 micrograms/L (normal range for age, 3.2 to 11.5 micrograms/L), and the IC-testosterone was 1.8 +/- 2.7 nmol/L. Two patients restudied during treatment had normal IC-GH values. After testosterone treatment, the mean IC-GH of the entire group was 3.3 +/- 2.6 micrograms/L, and the IC-testosterone was 6.5 +/- 5.3 nmol/L. Five of eight patients had IC-GH values that were again subnormal. A subnormal IC-GH associated with CD may persist after testosterone therapy is discontinued. Deficiency of spontaneous GH secretion may contribute to short stature and slower growth rates in this patient group. Whether GH therapy in these patients would have a beneficial effect on final height is unknown.

Child↗
PubMed1992

Effects of testosterone on growth hormone secretion and somatomedin-C generation in prepubertal growth hormone deficient male patients.

1. The role of testosterone (T) in growth was evaluated in 11 prepubertal hypopituitary males during two 15-day periods separated by a 4-week interval, i.e., before (PRE-T period) and during T ester treatment (50 mg every 5 days, 3 im doses-T period). 2. T increased growth hormone (GH) secretion, assessed by 4-h rhythm (mean +/- SEM = 1.90 +/- 0.27 vs 1.77 +/- 0.21 ng/ml; P < 0.05) and after a GHRH stimulus (3.42 +/- 0.54 vs 3.08 +/- 0.43 ng/ml; P < 0.05) as compared to the PRE-T period. 3. T also increased basal somatomedin-C (SM-C) levels (0.20 +/- 0.03 vs 0.15 +/- 0.02 U/ml; P < 0.001) and SM-C generation. After GH was administered in 4 im doses (0.01, 0.02, 0.05 and 0.1 U/kg), SM-C levels were 0.31 +/- 0.08 vs 0.24 +/- 0.07 U/ml, P < 0.001. T did not change incremental (absolute minus basal) SM-C levels (0.15 +/- 0.08 vs 0.12 +/- 0.07 U/ml; P > 0.05). 4. The results suggest that T increased plasma SM-C levels by stimulating residual GH secretion in hypopituitary males.

Adolescent↗
PubMed1985

Effect of naloxone on gonadotropin secretion before and after testosterone in Klinefelter's syndrome.

A study was performed on eight subjects with Klinefelter's syndrome to assess the relation between gonadal hormones and opioid inhibition of gonadotropin secretion through comparison of their gonadotropin response to naloxone (NAL) (0.3 mg/kg; 1/3 bolus iv. at time 0 and 2/3 iv. for 120 min) before and after testosterone propionate (TP) 100 mg/day im. for 5 days. Under basal conditions, NAL failed to induce a significant change in LH levels. After TP, however, despite unchanged basal LH levels (mean +/- S.E.M.: 27.0 +/- 3.4 vs 21.2 +/- 3.21 microU/ml), LH significantly increased in response to NAL. FSH did not respond to NAL either before or after TP administration, though FSH levels were significantly reduced by TP. These findings suggest that in man, as in animals, gonadal hormones regulate opioid inhibition of LH secretion. The negative feedback of testosterone and its ability to activate opioid inhibiting tone may be dissociated, in keeping with the view that gonadal hormones control gonadotropin secretion through the activation of distinct, albeit concomitant, mechanisms.

Adolescent↗
PubMedDate not supplied

Testosterone feedback on gonadotropin secretion and gene expression in transgenic mice expressing human growth hormone gene.

To determine the effects of testosterone on the regulation of gonadotropins in metallothionein-1/human growth hormone (MT/hGH) transgenic mice, basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from incubated pituitaries, as well as pituitary content of LH, FSH, and mRNA for their respective beta subunits, were measured in normal and transgenic males that were injected with testosterone propionate (5 micrograms/g body weight; 24 hours before autopsy), injected with oil vehicle, castrated for 10 days, or sham operated. In normal (non-transgenic) males, exogenous testosterone induced the expected suppression, and castration induced the expected stimulation of various parameters of gonadotropin synthesis and release. In contrast, in testosterone-treated and in castrated MT/hGH transgenic mice the release of LH and the pituitary levels of LH-beta mRNA did not differ from the corresponding values measured in vehicle-injected and sham-operated transgenic controls. Pituitary LH content was elevated in testosterone-treated MT/hGH transgenic mice but was not changed in castrated transgenic males. The changes in pituitary levels of FSH and FSH-beta mRNA and in FSH release in MT/hGH transgenic mice in response to testosterone and castration were different from the changes in LH and LH-beta mRNA in the same mice, but similar to the changes of FSH and FSH-beta message produced in normal mice by identical treatments. We suggest that hGH expression attenuates the effects of testosterone on the mechanisms controlling LH release, with less influence on testosterone regulation of LH synthesis. These effects of hGH expression appear to be selective for LH, without influencing the FSH control system.

Animals↗
PubMed1993

Gonadal differentiation and secretions of estradiol and testosterone of the ovaries of Rana catesbeiana tadpoles treated with 4-hydroxyandrostenedione.

Laparotomized female tadpoles of Rana catesbeiana at TK stages X-XII, about 9 months old, were implanted intraperitoneally with empty capsules or capsules containing 4-hydroxyandrostenedione (4-OHA), known as an aromatase inhibitor in vertebrates. Histology, gonosomatic index, and secretions of estradiol (E2) and testosterone (T) of the ovaries were investigated. Three months after the treatment, histological examination revealed various degrees of sex reversal in the ovaries treated with 4-OHA and 79% (57 in 72) were transformed into testes. The ovaries of control tadpoles, however, displayed normal histological appearance. Radioimmunoassay showed that secretion of E2 was decreased while that of T was increased in 4-OHA treated ovaries. The gonosomatic index displayed a decline tendency from control females through experimental animals to untreated control males. These results indicated that activity of aromatase in the ovaries was inhibited by 4-OHA, resulting in accumulation of T which induced transformation of the ovaries into testes.

Androstenedione↗
PubMed1983

Inhibition of polyamine synthesis blocks urinary secretion of beta-glucuronidase from mouse kidney.

The effect of inhibition of polyamine synthesis on castrated male mouse kidney beta-glucuronidase induction and secretion by testosterone was studied. Inhibition of the activities of polyamine synthesis key-enzymes, L-ornithine and S-adenosyl-L-methionine decarboxylases, was performed with the combined treatment of 2-difluoromethylornithine and methylglyoxal' bis(guanylhydrazone). Blockage of polyamine synthesis did not affect testosterone-induced increase in renal beta-glucuronidase but blocked its secretion into the urine. After withdrawal of inhibitor-treatment beta-glucuronidase secretion normalized, and repeated testosterone administration produced undisturbed beta-glucuronidase secretion peak in urine suggesting that blockage of beta-glucuronidase secretion was not due to the tissue damage produced by inhibitors. These results indicate that the stimulation of renal polyamine synthesis by testosterone is not necessary for the induction of beta-glucuronidase but is required for the urinary secretion of this protein.

Animals↗
PubMed1983

Hormonal control of hamster ear sebaceous gland lipogenesis.

The sites and hormonal control of lipogenesis in hamster ear sebaceous glands are reported. Sebaceous lipogenesis was determined in ear biopsies by incubation with glucose and tracer concentrations of 14C-acetate in buffer. The 14C-labeled lipids were saponified, extracted, and determined by liquid scintillation counting. Histologically, the ears contained many sebaceous glands. The glands of male animals were much larger and more heavily lipid-stained than glands from females. Lipogenesis was almost entirely confined to the sebaceous glands in the dermal stroma. Lipogenesis was considerably higher in ear biopsies from male hamsters than from female, castrate male, or hypophysectomized male hamsters. In contrast to published data using hypophysectomized rats, where dihydrotestosterone potently and testosterone only weakly increased sebum secretion, both testosterone and dihydrotestosterone potently increased lipogenesis in the ears of hypophysectomized male hamsters. Dihydrotestosterone was somewhat more potent than testosterone in the hamster. Hypophyseal hormones do not appear to be essential for androgen stimulated lipogenesis in the hamster. In female hamsters, 5 alpha-androstane-3 alpha, 17 beta-diol, testosterone, dihydrotestosterone, 4-androstene-3,17-dione, and 5 alpha-androstane-3,17-dione produced dose-dependent increases in lipogenesis. From this and other studies, it is suggested that androgens other than dihydrotestosterone could be physiologically important in man and animals in stimulating lipogenesis in sebaceous glands.

Androgens↗
PubMed1998

Androgens and masculinization of genitalia in the spotted hyaena (Crocuta crocuta). 1. Urogenital morphology and placental androgen production during fetal life.

According to common understanding of sexual differentiation, the formation and development of a penile clitoris in female spotted hyaenas requires the presence of naturally circulating androgens during fetal life. The purpose of the present study was to determine potential source(s) of such fetal androgens by investigating the timing of urogenital development and placental production of androgen during early and mid-gestation. Fetuses determined to be female by molecular techniques (lack of SRY gene) at days 33 and 48 of gestation had undifferentiated gonads, but the clitoris was already 'masculinized' and was generally similar to the phallus of a 50-day-old male fetus. Wolffian and Müllerian ducts terminated at the urogenital sinus in both sexes and a urethra was present along the entire length of the clitoris and penis. The adrenal gland was large and histologically differentiated at 33 days. Steroid gradients across the uterus (a drop in delta 4-androstenedione, with increases in oestrogen and androgen), and high androstenedione in ovarian veins indicated that ovarian androstenedione was metabolized and secreted as testosterone by the placenta throughout gestation. In vitro, whole or homogenized placentae at days 48 and 58 of gestation (110 days total) metabolized radiolabelled androstenedione into testosterone and oestradiol; the specific enzymatic activity of early placental tissues was higher than at later stages. A human placental homogenate had higher aromatase activity but did not produce testosterone unless aromatase was inhibited. Infusion of labelled androstenedione into the uterine arteries of hyaenas demonstrated the conversion of this substrate into testosterone and oestradiol and their secretion into the fetal circulation. Evidently, androgen is produced by the placenta and secreted into the fetal circulation from early in pregnancy when masculinization is first evident, before differentiation of the fetal ovary.

Androgens↗