Age-related changes in the concentration of cytosolic androgen receptors in the epididymis, vas deferens and seminal vesicle of maturing male mice.

In this study, changes in the number of androgen binding sites that occur in cytosols of epididymis, vas deferens and seminal vesicle of mice from 10 to 90 days of age are described. Specific saturable binding of [3H]R-1881 by cytosols of the three organs at all time points studied and age-related differences in the number of binding sites measured were observed. Cytosolic androgen receptor levels in all three organs studied were found to decrease with increasing age, regardless of whether the binding was expressed relative to weight of tissue, cytosolic protein or cellular DNA. The most pronounced change in androgen receptor levels (from 442 to 50 fmol/mg protein) was observed in the epididymis between 10 and 30 days of age. In these three organs there was no significant correlation between androgen (testosterone + dihydrotestosterone) levels and the concentration of androgen binding sites.

Long-term alterations on the male mouse genital tract associated with neonatal exposure to cyproterone acetate biochemical data.

The effects of neonatal administration of cyproterone acetate on the growth, hormone responsiveness, DNA and protein concentrations, protein profiles, protein synthetic patterns and nuclear androgen binding sites of epididymis, vas deferens and seminal vesicles were investigated in adult mice. The weight of epididymis and seminal vesicle was significantly depressed and the reductions observed were secondary to cellular hypoplasia in epididymis and to cellular hypotrophy in seminal vesicle. The 3 organs studied showed a limited response to exogenous androgens at adulthood. When assessed by the number of cells the response of the 3 organs was similar to that of controls but it was significantly reduced from 25 to 35% when measured in term of cellular concentration of proteins. The protein profiles from homogenates of whole organs and the protein synthetic patterns after [35S]methionine incorporation, analyzed by polyacrylamide gel electrophoresis, showed reproducible persistent alterations. The total number of nuclear androgen binding sites was significantly reduced in seminal vesicles.

Prolonged influence of a neonatal cyproterone acetate treatment on renal androgen binding in mice.

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 +/- 200 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.

Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens.

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.

Regional differences in the testosterone to dihydrotestosterone ratio in the epididymis and vas deferens of adult mice.

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 +/- 8.0 ng/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.

Imprinting of male sex tissues by neonatal endogenous androgens in mice. Molecular alterations following exposure to cyproterone acetate.

This study was conducted to evaluate the growth and biochemical responsiveness of the epididymis, vas deferens and seminal vesicles of adult mice exposed to cyproterone acetate during the first 10 days of life. Results indicate that the weight and protein content of sex accessory organs were significantly depressed, testosterone and dihydrotestosterone concentrations were unaffected or increased, the number of cytosolic androgen-binding sites was slightly or significantly reduced. The efficiency of exogenous testosterone in promoting growth and protein synthesis in target organs of castrated adult males was significantly lowered by neonatal cyproterone acetate treatment. It is concluded that a deficient androgenic stimulation during neonatal life induces a limited response of sex target organs to endogenous or exogenous androgens in adulthood.

[Ultrastructural study of the pseudopregnant rat luteal cell following the effect of luteinizing hormone and of 2 inhibitors of synthesis (amino-glutethimide and cycloheximide)]. / Etude ultrastructurale de la cellule lutéale de la ratte pseudogestante après action de l'hormone lutéinisante et de deux inhibiteurs de synthèse (aminoglutéthimide et cycloheximide

Incubation of ovaries from pseudopregnant rats have been performed with the gonadotropin LH and with two inhibitors, aminoglutéthimide and cycloheximide for periods comprised between 1 and 6 hours. Then the luteal cells have been studied with electron microscope. Measurements in have been used to express the variations in volume of two organels, mitochondria and lipid droplets. The principal modifications induced by these compounds bear on the mitochondria. Treatment with LH is followed by an increase in the volume of individual mitochondria resulting probably of fusion of organels. Treatments with the inhibitors are followed by reduction in the volume of individual mitochondria and in the total volume of mitochondrial apparatus. Mixed treatments using LH and an inhibitor allow to obtain organels of intermediate size. Volume of lipids is increased by incubation with LH and probably decreased by the inhibitors. Smooth endoplasmic reticulum shows rearrangements with the various treatments. It seems not convenient to extend incubations over 4 hours in order to avoid cytolysis.