Inhibition of 5α-reductase activity by natural and synthetic steroids in cultured human genital skin fibroblasts

1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S205-S206 ◽  
Author(s):  
E. JUNGLAS ◽  
G. ROMALO ◽  
H.U. SCHWEIKERT
Keyword(s):  
Reductase Activity ◽  
Skin Fibroblasts ◽  
Synthetic Steroids ◽  
Natural And Synthetic

Binding of androgens in 5α-reductase-deficient human genital skin fibroblasts: inhibition by progesterone and its metabolites

1982 ◽  
Vol 94 (3) ◽  
pp. 415-427 ◽  
Author(s):  
M. B. Hodgins
Keyword(s):  
Androgen Receptor ◽  
Androgen Receptors ◽  
Cultured Cells ◽  
Reductase Activity ◽  
External Genitalia ◽  
Skin Fibroblasts ◽  
Urogenital Sinus ◽  
Receptor Complexes ◽  
High Affinity ◽  
Receptor Sites

Binding of [3H]testosterone and 5α-dihydro[3H]testosterone ([3H]DHT) to specific androgen-receptor sites of 5α-reductase-deficient human genital skin fibroblasts (five cell-lines) was studied in the intact cultured cells at 37 °C. Under the conditions of the experiments, conversion of [3H]testosterone into [3H]DHT was negligible. Both steroids bound to the same set of high-affinity saturable sites in cytoplasmic and nuclear fractions of the cells. Unlabelled testosterone, DHT and methyltrienolone competed effectively with the labelled steroids. Progesterone and oestradiol were weaker competitors; cortisol did not compete. The dissociation constant (Kd) for high-affinity complexes with [3H]testosterone (0·44 ± 0·035 nmol/l) was higher than that for [3H]DHT complexes (0·20 ± 0·090 nmol/l). Unlabelled DHT was more effective than unlabelled testosterone in competing with either radioactive steroid. Complexes of [3H]DHT and receptor dissociated more slowly than [3H]testosterone-receptor complexes and [3H]DHT bound more extensively to low-affinity non-saturable sites in fibroblasts. As judged by competition with the radioactive androgens, progesterone bound to the androgen receptor with a Kd of about 7 nmol/l. 5α-Pregnane-3,20-dione had an approximately fivefold lower affinity than progesterone for androgen receptors; 3α/β- or 20α-reduction lowered its affinity further. It is suggested that in 5α-reductase deficiency in man, progesterone in amniotic fluid and blood could effectively inhibit testosterone binding to androgen receptors in the male embryonic external genitalia. One function of the high levels of 5α-reductase activity normally found in embryonic external genitalia and urogenital sinus may be to protect these tissues from the potentially antiandrogenic action of progesterone.

Androgen Binding Capacity and 5α-Reductase Activity in Pubic Skin Fibroblasts from Hirsute Patients*

1983 ◽  
Vol 56 (6) ◽  
pp. 1209-1213 ◽  
Author(s):  
Irene Mowszowicz ◽  
Evie Melanitou ◽  
Abiba Doukani ◽  
Françoise Wright ◽  
Frederique Kuttenn ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Reductase Activity ◽  
Skin Fibroblasts ◽  
Androgen Binding

scholarly journals Mitochondrial NADH- or NADPH-Linked Aquacobalamin Reductase Activity Is Low in Human Skin Fibroblasts with Defects in Synthesis of Cobalamin Coenzymes

1996 ◽  
Vol 126 (12) ◽  
pp. 2947-2951 ◽  
Author(s):  
Fumio Watanabe ◽  
Hisako Saido ◽  
Ryoichi Yamaji ◽  
Kazutaka Miyatake ◽  
Yuji Isegawa ◽  
...  
Keyword(s):  
Human Skin ◽  
Reductase Activity ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts

Influence of Certain Natural and Synthetic Steroids on Genital Development in Guinea Pigs

1968 ◽  
Vol 19 (4) ◽  
pp. 606-615 ◽  
Author(s):  
W. Darrell Foote ◽  
Warren C. Foote ◽  
Leonard H. Foote
Keyword(s):  
Guinea Pigs ◽  
Genital Development ◽  
Synthetic Steroids ◽  
Natural And Synthetic

Influence of steroid hormones on 5α-reductase activity in female and male genital skin fibroblasts in culture

1993 ◽  
Vol 128 (2) ◽  
pp. 161-167 ◽  
Author(s):  
MW Beckmann ◽  
P Wieacker ◽  
MM Dereser ◽  
U Flecken ◽  
M Breckwoldt
Keyword(s):  
Steroid Hormones ◽  
Reductase Activity ◽  
Feedback Mechanism ◽  
Skin Fibroblasts ◽  
Cellular Regulation ◽  
Physiological Regulation ◽  
Negative Feedback Mechanism ◽  
Male Patients ◽  
Female Genital ◽  
Male Genital

The physiological regulation of 5α-reductase (5αR) as well as the complex pathogenesis of male and female androgenic disorders are still incompletely understood. Therefore, we examined the influence of various steroid hormones on the 5αR activity in female and male genital skin fibroblasts in primary culture to test whether the 5αR activity is identically regulated in genital skin samples of both sexes. Nine foreskin samples of male patients and 11 specimens of female genital skin were prepared and cultured as primary tissue cultures. After pre-incubation with various unlabeled steroids, [3H]-testosterone was added to the cultures and the 5αR activity (conversion of testosterone to dihydrotestosterone) measured. (a) The pre-incubation of male foreskin fibroblasts with unlabeled androstenedione and androstandione both resulted in stimulation of 5αR activity. Other unlabeled steroid hormones, including progesterone, testosterone, dihydrotestosterone, and estradiol had no significant effect on 5αR activity. (b) In female genital skin fibroblasts, pre-incubation with testosterone also led to an increase in 5αR activity, whereas pre-incubation with estradiol decreased 5αR activity. None of the other unlabeled steroid hormones applied had significant effects. These data on male foreskin in culture suggest a physiologic regulatory mechanism of 5αR activity independent of the concentration of the enzymatic substrate or product, whereas the results for the female genital skin suggest a cellular regulation of the androgen levels by the enzymatic substrate testosterone and a possible negative feedback mechanism of estrogens. Furthermore, the data suggest that the 5αR activity regulation of genital skin fibroblasts is different in female and male.

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