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G. Veyssiere, Ch. Jean-Faucher, M. Berger and Cl. Jean

Abstract.

Studies were conducted to evaluate the effects of neonatal administration of supraphysiological doses of testosterone on the growth, hormone responsiveness, DNA and protein content, and protein profiles of the epididymis, vas deferens and seminal vesicles in adult mice. Results indicate that in androgenized males, testicular growth (DNA and protein content), circulating and organ androgen levels, and fertility were significantly depressed. The weights of the epididymis, vas deferens, seminal vesicle and kidney, but not that of the spleen, were significantly diminished subsequently to a reduction of protein (all organs) and DNA (epididymis, vas deferens) content. The efficacy of testosterone in promoting accessory sex organs and kidney growth, in adult castrated males, was persistently reduced in neonatally androgenized males. When assessed by DNA content, the response of all organs (except the seminal vesicle) was similar to that of controls, but it was significantly reduced from 16 to 43% when measured in terms of protein content. The protein profiles from seminal vesicles and vas deferens analysed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations which could be reversed by adult androgen therapy.

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G. Veyssière, M. Berger, Ch. Jean-Faucher, M. de Turckheim and Cl. Jean

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.

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G. Veyssiere, M. Berger, Ch. Jean-Faucher, M. de Turckheim and Cl. Jean

Abstract.

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).

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Ch. Jean-Faucher, M. Berger, M. de Turckheim, G. Veyssiere and Cl. Jean

ABSTRACT

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 days

Testosterone 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.

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M. de Turckheim, M. Berger, Ch. Jean-Faucher, G. Veyssière and Cl. Jean

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, E2 was already quantifiable in ovaries; it remained at very low levels up to 50 days. Ovarian E2 content 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). E1 appeared 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.

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G. Veyssiére, Ch. Gallon, M. Berger, Ch. Jean-Faucher, M. de Turckheim and Cl. Jean

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.

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Ch. Jean-Faucher, N. El Watik, M. Berger, M. de Turckheim, G. Veyssière and Cl. Jean

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.

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M. Berger, Ch. Jean-Faucher, M. De Turckheim, G. Veyssière and CI. Jean

Abstract.

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.

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M. Berger, Ch. Jean-Faucher, M. de Turckheim, G. Veyssiere, M. R. Blanc, J. C. Poirier and Cl. Jean

Abstract.

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.