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Synthesis and secretion of T and DHT by 18, 19 and 20 day old foetal rabbit testes were measured (RIA) in an organ culture system (M199). It was demonstrated that synthesis and secretion in vitro of T and DHT were greater at 19 and 20 days than at 18 days. The T and DHT production could be stimulated by ovine LH at 19 and 20 days but not at 18 days. The pituitaries of 19 and 20 day old male and female foetuses (but not those of foetuses aged 18 days) stimulate synthesis and secretion of T by 20 day old testis. A gonadotrophic factor, active on testicular T production, is present in the pituitary gland of 19 day old foetuses of both sexes.These findings indicate that the testicular responsiveness to LH and to the pituitary appears concomitantly with the pituitary gonadotrophic activity, between 19 and 20 days, just prior to the beginning of male sexual differentiation (20–25 days).

Sexual maturation was evaluated in male mice subjected to prenatal and preweaning overnutrition induced by reduction of litter size in embryonic and post-natal life. From birth to adulthood body weight was higher in overfed males than in controls. Plasma and testicular testosterone levels followed a similar pattern in normally fed and overfed males. Adult gonadotrophin levels were attained at 30 (FSH) and 40 (LH) days in controls and as soon as 20 days in overfed males. First fertile ma-tings occurred at the same age in both groups. Overnourished males attained puberty when weighing considerably more than controls (34.7 ± 0.4 vs. 29.4 ± 0.3 g). The 30-day-old overfed males, which have attained the critical pubertal body weight of controls, were sexually immature.The data showed that in male mice puberty does not seem to be triggered by the attainment of a critical body weight.

Experiments were designed to examine the influence of either one or both parents on the sexual maturation of male mice. A pregnant female and an adult vasecto-mized male were housed together and, at delivery, the litter was reduced to 6 pups, 3 of each sex. After weaning, mother, foster-father or both, stayed in cohabitation with their pups until sacrifice. The results showed that : (1) the permanent presence of one or both parents did not affect either testicular growth or the age at first fertile matings. (2) in maturing males (30-40 days), seminal vesicle growth was accelerated by the presence of the mother, inhibited by the presence of the foster-father. (3) in maturing males, the presence of one or both parents lowered plasma testosterone levels. On the opposite, in 90-day-old males, the same conditions increased testosterone levels.

Abstract. Plasma LH and FSH concentrations were determined by radioimmunoassay in male mice from birth to adulthood after LRH injection, castration and testosterone replacement therapy. Except at birth for LH, LRH significantly increased circulating levels of both gonadotrophins at all stages studied. It is suggested that a change in the pituitary LH response to LRH occurs around puberty and perhaps represents the time of initiation of pubertal processes. At all stages studied (except the infantile stage for LH) castration resulted in a significant rise in circulating LH and FSH levels. The magnitude of LH response to castration increased with age but not that of FSH. Testosterone replacement therapy, inducing supra-physiological circulating testosterone levels, was ineffective to depress the post-castration rises of LH and FSH levels.

Summary.The concentrations of testosterone and dihydrotestosterone (DHT) were measured in the testis and in different segments of the epididymis and vas deferens of adult mice. There were marked regional variations in the concentrations of testosterone and DHT from the testis to the caudal part of the vas deferens. In the testis, testosterone was the predominant androgen (364 ± 90 ng/g) while DHT was weakly represented (8 ± 2 ng/g). Qualitative and quantitative changes occurred in epididymis: DHT was the main steroid in the caput (29·3 ± 2·7 ng/g) and corpus (33·1 ± 4·4 ng/g) while testosterone and DHT were in similar quantities in the cauda (18·6 ± 2·6 and 19·0 ± 2·7 ng/g, respectively). The proximal region of the vas deferens contained higher amounts (71·4 ± 8·0ng/g) of androgens (testosterone + DHT) than did the caput epididymidis (39·1 ± 3·3 ng/g). Testosterone was the predominant androgen in each part of the vas deferens and its concentrations decreased from the proximal (64·5 ± 7·5 ng/g) to the caudal (26·9 ± 4·3 ng/g) region. Castration and section of the efferent ducts of the testis showed that the epididymis received testosterone essentially via the blood supply and that epididymal DHT was produced locally from circulating testosterone.

Male mice were raised in populations of two different sizes from birth to adulthood: six animals (three of each sex) or 30 animals (15 of each sex) being maintained in cages of the same dimensions. Animals were killed every 10 days from weaning to 60 days and at 90 days. Increased population size induced decreased body and seminal vesicle weights; testicular, pituitary and adrenal weights were little affected. Plasma testosterone levels were lowered by increasing population size over the period from weaning to 50 days but they were increased at 60 and 90 days. The age at which first fertile matings occurred was not affected. These results indicate that the endocrine function of the testis, as determined by the measures used here, was specifically affected by this differential housing.

To study the ontogenesis of fetal pituitary gonadotrophin synthesis and release, LH and FSH were measured by radioimmunoassay in fetal rabbit pituitary glands and blood of both sexes from day 18 of gestation until birth. Results on levels of testicular and plasma testosterone were also included. Immunoreactive LH was first detected on day 19 in the pituitary gland and on day 20 in the plasma of fetuses of both sexes. Pituitary FSH was first measurable in both male and female fetuses at 24 days of gestation. Levels of FSH could not be detected in the blood of male fetuses at any time during gestation. In females, FSH could be measured in the circulation from day 27 of gestation until birth.These results show that (1) the ontogeny of pituitary LH and the onset of testosterone secretion are closely correlated and take place between 18 and 20 days of gestation just before the beginning of differentiation of the male genital tract, and (2) the highest concentrations of pituitary LH and FSH are observed, in both sexes, in late gestation after days 24–25.

Abstract. Plasma oestrogens (E1, E2) and gonadotrophins, and ovarian oestrogens, were determined in female rabbits from birth to 6 months. Increases in ovarian weight followed a curvilinear pattern, with a phase of slow growth (from 1 to 60 days) preceding a phase of rapid growth (from 60 to 90 days). At birth, E2was already quantifiable in ovaries; it remained at very low levels up to 50 days. Ovarian E2content increased until 6 months with two sharp rises between 50 days (46 ± 4 pg/2 ovaries) and 60 days (365 ± 53 pg/2 ovaries) and between 80 days (326 ± 77 pg/2 ovaries) and 90 days (1118 ± 307 pg/2 ovaries). E1appeared in ovaries at 50 days and then followed a pattern similar to that of E2. Oestrogens were never detected in plasma.At birth FSH and LH levels were similar to those measured in adult females but from 10 days the secretion of both gonadotrophins showed a clear dissociation. LH concentrations varied little during the period studied (between 1077 ± 106 pg/ml to 2030 ± 466 pg/ml). Plasma FSH levels were considerably higher between 10 and 50 days than those measured thereafter, particularly in adulthood. The decline in FSH levels occurred simultaneously with the rise in ovarian oestrogens.

Testosterone was measured every 10 days in plasma and testes of male rabbits, from birth to 90 days of age. Plasma testosterone varied little from birth (3.8 ng/10 ml) to 40 days (4.6 ng/10 ml) and increased thereafter until the 60th day (40.1 ng/10 ml). This level, characteristic of puberty, remained unchanged until the 90th day and decreased thereafter. Testicular testosterone content followed a similar pattern. It remained steady from the 1st to the 20th day. From the 20th day to the 50th day it rose slowly. Between the 50th and 60th day it increased rapidly and reached its maximum at the 60th day (339.8 ng). It remained at the same level until the 90th day. Testicular testosterone concentration was steady from 1 to 20 days, then increased quickly, reaching a maximum at 60 days (154.8 ng/100 mg). It then decreased until the 90th day (48.4 ng/100 mg).

Abstract. To determine whether neonatal endogenous androgens influence adult renal androgen binding, newborn male mice were injected from 1 to 10 days of age with cyproterone acetate and newborn females with testosterone from 1 to 10 days and from 20 to 40 days of age. In controls, at adulthood, the total cellular androgen receptor content was significantly higher in males (1700 200 receptors per cell) than in females (1060 ± 50) and, as expected, the nuclear receptor content was 12-fold higher in males. While the total number of receptors (1650 ± 220 per cell) was unchanged in adult males neonatally treated with cyproterone acetate, their distribution between cytosol and nucleus was similar to that in control females despite normal circulating and renal testosterone levels. The nuclear receptors represented 50, 7 and 11% of the total receptors in control males, control females and cyproterone acetate-treated males, respectively. The very low levels of nuclear receptors present in the kidney of cyproterone acetate-treated males probably explain the decreased sensitivity of this organ to testosterone. The nuclear receptor accumulation measured in adult animals after a single injection of testosterone did not seem to be affected by neonatal hormonal manipulations.

Abstract. Pituitary and testicular function was studied in pubertal and adult rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone. Circulating testosterone, LH and FSH levels showed a developmental pattern during sexual maturation, similar to that observed in controls. Plasma FSH levels were elevated in male pseudohermaphrodites despite normal plasma testosterone concentrations. Fighting, male sexual behaviour and coitus occurred normally as in controls.The testicular response to endogenous elevated LH levels and the pituitary LH and FSH responses to LRH injection and to castration were similar in affected males and in controls. These observations suggest that inhibition of the central effects of androgens during the embryonic and perinatal period has little or no effect on the differentiation and maturation of the hypothalamo-pituitary-testicular axis in rabbit.

Male rabbits were castrated at infantile (30 days), peripubertal (60 days) and adult (7–8 months) stages. Two different doses of testosterone were injected 10 days after castration (5 injections at 12 h intervals). Plasma LH and FSH were determined by RIA 1,5 and 10 days after castration and 1 h after the last injection of testosterone. The response of both gonadotrophins to castration was age-dependent. In 30 day old castrated males LH was not significantly modified and FSH had increased only 10 days after castration. In 60 day old and adult males FSH and LH levels were increased 24 h after castration and continued to rise as time progressed. For both gonadotrophins, the response of adult males to castration was higher than that of immature animals. At all stages studied, the highest dose of testosterone (250 μg/kg body weight) depressed post-castration LH and FSH levels. Twenty-five μg of testosterone per kg body weight was effective to depress LH levels only in 30 day old males, suggesting a change in the hypothalamic-pituitary unit to the negative feedback of androgens.These findings suggest that there are marked changes in the hypothalamic-pituitary unit around the beginning of the peripubertal stage. These changes could play a determinant role in the onset of puberty.

Male mice were raised in cohabitation with females from birth to 90 days. Testosterone was measured every 10 days in plasma and testes. Sex difference in body weight was related to the pre-pubertal increase of testosterone levels in males. The weight of the seminal vesicle was positively correlated with circulating testosterone levels between 1 and 40 days but not between 50 and 90 daysTestosterone concentrations in the plasma and testes were high at birth: 630 pg/ml and 58.0 ± 17.7 ng/100 mg; they subsequently decreased during the first days of life and remained low until day 20: 240 ± 110 pg/ml and 0.1 ± 0.03 ng/100 mg. The testosterone levels then increased rapidly between days 20 and 30 and especially between 30 and 40 reaching their maxima: 5770 ± 1720 pg/ml and 123.7 ± 18.3 ng/100 mg testis. This increase was transitory and testosterone levels fell after day 40. By 90 days, the testosterone levels, 440 ± 65 pg/ml and 43.2 ± 5.5 ng/100 mg testis, were comparable to those measured at birth. Plasma testosterone and age were positively correlated between 1 and 40 days, and negatively between 50 and 90 days.The first fertile matings occurred at age 40 days.

Cyproterone acetate was administered every 2 days from 1 to 39 days of age to male mice which were killed 24 h or 20 days after the last injection. Cyproterone acetate caused a significant reduction in the relative weights of the epididymis, vas deferens, seminal vesicle and preputial gland, which was still evident at 60 days after birth. Testicular and epididymal androgens (testosterone and dihydrotestosterone) and circulating LH and FSH concentrations were equal to or higher than those of controls at 60 days. Cyproterone acetate did not inhibit spermatogenesis but all males were infertile. The results suggest that the peripheral effects of testosterone are necessary, during early stages of sexual maturation, in order to obtain subsequent full development of the accessory sex organs.J. Endocr.(1984) 102, 103–107

Young sexually naive (3-4 months) and sexually experienced (2-3 years) male rabbits were subjected to various sexual stimulation procedures. Blood samples were taken just before and 30 min after mounting (unreceptive females) or coitus (receptive females). Testosterone and luteinizing hormone were assayed using specific radioimmunoassays. Sexual stimulation did not affect postcoital testosterone and LH levels in naive and experienced males while in females LH levels were significantly increased.We may conclude that the postcoital neuroendocrine reflex which causes a massive release of pituitary LH in female rabbit does not exist in males.

Male mice were injected daily with cyproterone acetate for 10 consecutive days during one of the four following periods: 1–10 days, 11–20 days, 21–30 days or 31–40 days. At all stages studied cyproterone acetate caused a significant reduction in the relative weights of epididymis, vas deferens, preputial gland and seminal vesicle in males killed 24 h after the last injection; the androgen content (testosterone + dihydrotestosterone) of the accessory sex organs was also reduced but the differences were not always significant. Cyproterone acetate treatment from 1 to 10 days resulted in a definitive reduction in the relative weights of all accessory sex organs studied and when injected from 11 to 20 days in epididymis and vas deferens. When cyproterone acetate was injected after 20 days of age, the inhibition of sexual organ weights was reversible and at adulthood organs were normally developed. Cyproterone acetate treatment induced a high percentage of infertile males only when injected from 1 to 10 days. Spermatogenesis, androgen levels in plasma and accessory sex organs, and sexual behaviour were not affected in sterile males.These results suggest that the functional development of accessory sex organs can be permanently affected by short-term neonatal exposure to endogenous androgens.J. Endocr.(1985) 104, 113–120

Kidneys of adult male mice are larger than those of females because of both cellular hyperplasia and hypertrophy. Administration of testosterone to adult female mice induced cellular hypertrophy but not hyperplasia, so that the weight of the kidney remained smaller than in male mice. The sexual dimorphism in kidney size is not congenital but programmed by neonatal endogenous androgens and expressed between 30 and 40 days of age. Treatment of newborn males with cyproterone acetate and of newborn females with testosterone induced female and male patterns of renal growth respectively. It appears that neonatal endogenous androgens are required to induce the characteristic cellular hyperplasia of the kidneys of male mice. Manipulation of androgen levels during neonatal and prepubertal life was found to affect the growth response of the kidney to androgens in adult male and female mice.J. Endocr.(1987) 115,241–246

Plasma testosterone, LH and FSH levels were determined and correlated with reproductive organs growth, testicular differentiation, fighting and mounting behaviour in maturing rabbit.An infantile phase of development extends from birth to 40 days, characterized by low testosterone and FSH levels, decreasing LH levels (until 20 days) and by a slow growth of testis and seminal vesicle. The peripubertal phase starts abruptly around day 40. It is marked by simultaneous events: the appearance of mature Leydig cells in the testis, a striking increase in testosterone and FSH levels, a small rise in LH levels and an acceleration of testicular growth. The phase of rapid growth of seminal vesicle and the first meiotic divisions start around day 70, in presence of high circulating levels of FSH and testosterone. Fighting (3 months) and mounting behaviour (146 ± 13 days) occur lately after a long period of high circulating testosterone levels.

The injection of pregnant mice with 5 mg oestradiol dipropionate induced a high proportion of bilateral cryptorchidism in the male offspring. The ectopic testes were reduced in size and occupied one of three different positions in the abdomen: pararenal, paravesicular or inguinal. The seminal vesicles were found to be similarly reduced in size whereas the adrenals and pituitaries appeared to be unaffected. The total content of testosterone was reduced in the pararenally placed gonads but was not significantly different from that of the controls when the testes were in the inguinal region. The content of androstenedione was not significantly altered. The concentration of both hormones, however, was increased in all cases. Plasma testosterone levels were lower in all the offspring of treated mothers, especially in those with high ectopia.