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Biomedical subjects

M A Drosdowsky

Publications and source records attributed to M A Drosdowsky.

At least 55 records · Page 3Linked to original sources

In vitro pregnenolone metabolism by mouse adrenal gland: II-Biosynthesis of androgens.

Adrenal gland homogenates from four different strains of mice were incubated with (4-14 C)-pregnenolone and a NADPH generating system. The most important androgen synthesized was dehydroepiandrosterone; testosterone and progesterone were synthesized to a lesser extent and the production of androstenedione was very low. The highest synthetic activities were found in the high mammary tumor strain of mice (C3H x RIII) Fl; they were increased by ovariectomy, particularly when performed at two months of age. In the other strains, they were lower, specially in the low mammary tumor strain C 57 BL. However, the 3 beta-hydroxysteroid dehydrogenase / delta 5, 4 isomerase activity was not modified by ovariectomy in the high mammary tumor strain whereas it was increased in the low mammary tumor strains. These results indicate that the androgen synthesis in mouse adrenal depends on factors such as age, sex, endocrine status (ovariectomy) but also on susceptibility to mammary tumor development.

Adrenal Glands↗

Hormonal regulation of androgen-binding protein in lamb testes.

Androgen-binding protein (ABP) was measured in the testes of 50-day-old lambs. The animals were hypophysectomized and treatment lasting for 5 days was begun 15 days after surgery. In hypophysectomized but otherwise untreated lambs (control group), no 5 alpha-dihydrotestosterone binding was detectable in testicular cytosol. One out of four lambs gave a positive response with FSH treatment (25 fmol ABP/mg protein), whereas a restoration of the synthesis of ABP was noted in all LH-treated animals (19 +/- 9 (S.E.M.) fmol ABP/mg, n = 4). No synergism between the two gonadotrophins was observed in lambs treated simultaneously with FSH and LH (19 +/- 4 fmol ABP/mg, n = 5). Testosterone treatment elicited a greater response (37 +/- 9 fmol ABP/mg, n = 5) than FSH or LH alone and the response was not increased by the simultaneous addition of FSH (38 +/- 10 fmol ABP/mg, n = 5). Whatever the treatment, no influence was observed either on the number of supporting cells (undifferentiated Sertoli cells) or the length of the seminiferous tubules (P>0.05); the diameter of tubules was significantly increased in the group treated with FSH and LH. It is postulated that testosterone may have a direct effect on the production of ABP by the supporting cells of the impuberal lamb.

Androgen-Binding Protein↗

Interactions between prolactin and ovarian secretions during mammary tumorigenesis in the mouse.

The plasma levels of ovarian steroids and the steroid binding capacity in the cytosol of mammary glands have been determined in the low-mammary-tumor C3H/f (XVII) mice. Implantation of a pituitary under the kidney leads to an increase of all these parameters as well as a high mammary tumor incidence. Simultaneous administration of the trans isomer of broparestrol (TBP) leads to a decrease of all the parameters.

Animals↗

Estradiol and progersterone receptors in F1 (C3H X RIII) mice mammary tumors: effect of castration.

The estradiol binding capacity has been determined in the cytosol of spontaneous mammary cancer in the high-mammary-tumor F1 (C3H X RIII) hybrid mice. This binding is modified neither during tumor growth nor after ovariectomy. Since these tumors do not regress after ovariectomy, they are classified as ovarian-independent for their growth, although their estradiol binding capacity is maintained, at its low initial level.

Animals↗

In vitro effects of prolactin and dexamethasone on rat Leydig cell aromatase activity.

In Percoll purified adult rat Leydig cells, the estradiol secretion, in presence of exogenous testosterone (200 ng/ml) is stimulated 2-fold by either LH (100 ng/ml) or dbcAMP (1 mM). The addition of prolactin (1 microgram/ml) or dexamethasone (10(-7) M) to the Leydig cell incubation medium induces a 20% increase of the basal estradiol production, whereas, under LH or dbcAMP stimulations, 46 and 41% decreases are noted; moreover, a synergistic effect between prolactin and dexamethasone was observed in presence of dbcAMP leading to a 53% diminution of the estradiol synthesis. There results suggest that either hyperprolactinemia or high doses of glucocorticoids might inhibit the Leydig cell aromatase activity in presence of LH.

Animals↗

Enzymatic properties of adult human Sertoli cells in vitro.

The adult human Sertoli cells produced lactate, estradiol-17beta, transferrin and inhibin; germ cells modulate synthesis of these compounds. In order to study the functional features of human Sertoli cells in vitro, the aim of this study was to measure the lactic dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and creatine kinase activities (CK) in primary cultures of Sertoli cells prepared from young men (mean age: 29 years, n = 11). Five LDH isozymes have been found in Sertoli cells, the main fractions being the LDH3 and LDH4; each of them represented 30% of the total LDH activity. Furthermore, CK and ALP activities were measured in Sertoli cells. It is of note that the Sertoli cell ALP activity was 50% lower than that of germ cells. Whatever the Sertoli cell parameter measured herein, there is a great variability between patients and FSH (dbc AMP, as well as retinol, insulin, testosterone) is poorly effective in improving these enzymatic activities in vitro. We have confirmed that GGT was exclusively present in Sertoli cells and thus may be considered as a specific marker. LDH is involved in Sertoli cell glucose transformation and thus provided energetic substrates for germ cells. In contrast, the roles of CK and ALP remains to be clarified. In conclusion, we have demonstrated the existence of several enzymes namely LDH, GGT, ALP and CK in Sertoli cells prepared from adult human testis.

Adult↗

Steroidogenesis in the two enriched-Leydig cell populations of human testis: evidence for a positive control by seminiferous tubules secreted factor(s).

In two different enriched populations of Leydig cells (called FI and FII) obtained from human testes (young patients: mean age 36 +/- 3 years, n = 6; aged men: mean age 73 +/- 2 years, n = 5), the dehydroepiandrosterone and testosterone in vitro outputs were increased in a dose- and time-related manners by hCG. Similar results were obtained when the Leydig cells were incubated in presence of either dbcAMP or 22R-hydroxycholesterol. In presence of either hCG or dbcAMP, the coefficient of stimulation (in terms of steroid outputs) was higher in FII when compared to FI. Conversely, the basal production of steroids was greater in FI than in FII, mainly for testosterone. The addition of increasing amounts of seminiferous tubule culture medium (STM) to the Leydig cell incubation medium led to a dose-related enhancement of the steroid production in both enriched-Leydig cell fractions under basal and hCG-stimulated conditions. Similar results were obtained in presence of increased seminiferous tubules length. Additional experiments realized with either concentrated STM or the coculture of seminiferous tubules with purified Leydig cells have confirmed the existence of a paracrine control of Leydig cell steroidogenesis by seminiferous secreted factor(s). A paracrine factor (or factors) from seminiferous tubular origin influences positively and with a high efficiency the Leydig cell function in humans, whatever the age.

Adult↗

[Testosterone metabolism in isolated cells of rat and ram seminiferous tubules].

Aspermatogenic seminiferous tubules were obtained from adult Wistar rats treated with Busulfan at the 20th day of foetel life. The isolated tubules converted 14C testosterone (T) into androstenedione (delta4), 3,5%) 5 alpha-dihydrotestosterone (DHT), (1%) ANd 5 alpha-androstane-3 beta, 17 beta-diol at unit gravity and incubated with 14C-T. Only delta was produced (2%). Using a similar technique the same result was obtained when pure preparation of round spermatids and primary spermatocytes from ram testis were incubated with 14C-T. From these experiments, we conclude that 5 alpha-reductase activity is present only in Sertoli cells.

Animals↗