3-alpha-Adiol

We report a mouse short-chain dehydrogenase/reductase (SDR), retinol dehydrogenase-similar (RDH-S), with intense mRNA expression in liver and kidney. The RDH-S gene localizes to chromosome 10D3 with the SDR subfamily that catalyzes metabolism of retinoids and 3 alpha-hydroxysteroids. RDH-S has no activity with prototypical retinoid/steroid substrates, despite 92% amino acid similarity to mouse RDH1. This afforded the opportunity to analyze for functions of non-catalytic SDR residues. We produced RDH-S Delta 3 by mutating RDH-S to remove an "additional" Asn residue relative to RDH1 in its center, to convert three residues into RDH1 residues (L121P, S122N, and Q123E), and to substitute RDH1 sequence G208FKTCVTSSD for RDH-S sequence F208-FLTGMASSA...

Isotretinoin, used to treat severe acne, has been shown to induce hormonal changes, especially to reduce 5 alpha-reductase in the production of the tissue-derived dihydrotestosterone (DHT) metabolite 3 alpha-Adiol G. However, the effects of isotretinoin on other pituitary, adrenal or gonadal hormones have not been thoroughly elucidated. In the present study, isotretinoin administered at a dose of 0.5 mg/kg/day for 4 weeks caused no marked changes in the serum levels of pituitary, adrenal or gonadal hormones or 3 alpha-Adiol G in patients with severe papulopustulotic acne (n = 19)...

The suppression of hyperinsulinism with diazoxide (300 mg/d during 30 days) in a young woman with PCOS and hirsutism, hyperinsulinism and insulinoresistance was followed by a modification of plasma androgens. Testosterone (T) and free testosterone (fT) were reduced after ten days and then increased but always remained below the baseline level. DHEAS had increased 200% by day 10, and 3 alpha-adiol G to three times its basal value by day 20. These modifications were constant during the treatment. fT decrease was secondary to reduction of hyperinsulinism which was followed by an increase of TeBG and a modest and transient reduction of androgen theca cells production...

The metabolism of dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) was assessed in full homogenates of rat prostate and epididymis. The major degradational route of DHT was catalysed by the enzyme(s) 3 alpha-hydroxysteroid oxidoreductase (HSOR). Enzyme kinetic characteristics Vmax, Km and Vmax/Km ratio, were obtained for the NADP(H)- and NAD(H)-dependent interconversion of DHT and 3 alpha-Adiol at pH 7.0 and at saturated co-factor concentration. For both the reduction of DHT and the oxidation of 3 alpha-Adiol, NAD(H) was the preferred co-factor when activities were rated by their Vmax and Vmax/Km ratio...

Functional differentiation of prostatic epithelium is manifested by the production of tissue specific secretory proteins. In vivo production of these proteins is dependent on the presence of serum androgens. A serum-free organ culture system was used to examine the initiation of prostatic epithelial cytodifferentiation in vitro using two rat prostate specific secretory proteins (DP-1 and probasin) as markers of epithelial cytodifferentiation. The dorsal-lateral and anterior prostatic (AP) lobes from 12-day-old rats were cultured for 6 days in serum-free medium in the presence or absence of androgens...

Two steroid 5 alpha-reductase isozymes designated type 1 and 2 synthesize 5 alpha-reduced androgens and other 5 alpha-reduced steroid hormones. Naturally occurring mutations in the gene encoding 5 alpha-reductase type 2 cause male pseudohermaphroditism, indicating that this isozyme is responsible for the synthesis of dihydrotestosterone required for virilization of the embryonic male urogenital tract. To determine the physiological role of 5 alpha-reductase type 1, homologous recombination in mouse embryonic stem cells was used to produce male and female mice with a disruption (null allele) in the type 1 gene (Srd5a1)...

It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]...

The conversion of dihydrotestosterone (DHT) to 3 alpha-androstanediol (3 alpha-adiol) was studied using the microsomal fractions of 15 hyperplastic, 5 malignant and 6 normal human prostatis tissues. Standard assay conditions were: 0.2 microM DHT, 1.0 mM NADPH, 1.0 mM NADH, 2.0 mM EDTA and the microsomal fractions equivalent to 200 mg of prostatic tissue, in 0.1 M MES buffer, pH 6.5. Under the conditions of this assay, the back-conversion of 3 alpha-adiol to DHT or the conversion of DHT to androstanediol were negligible...

Androgen metabolism and the regulation of rat ventral prostate cell proliferation and secretory function were examined during sexual maturation. Changes in acid phosphatase (AP) characteristics were measured as a marker of androgen-dependent prostatic secretory function. In immature (21-day-old) rats, total AP activity per cell was low (14.2 +/- 1.3 mol p-nitrophenol phosphate hydrolysed/h per mg DNA); it increased threefold as the weight, protein and DNA contents of the prostate increased to adult (65-day) levels...

Castrated male rats were treated with constant-release implants filled with testosterone, oestradiol-17 beta, 17 beta-hydroxy-5 alpha-androstan-3-one (5 alpha-dihydrotestosterone; DHT), 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) or 5 alpha-androstane-3 beta,17 beta-diol (3 beta-Adiol). Only testosterone activated the sexual behaviour of the rats. If combined with oestradiol, DHT or 3 alpha-Adiol induced the behaviour, but 3 beta-Adiol failed to have this effect. Oestradiol inhibited the in-vitro formation of [14C]Adiols from [14C]DHT by combined preoptic and hypothalamic tissue, but only when given in high doses...

Serum 3 alpha-androstanediol glucuronide (3 alpha-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3 alpha-Adiol-G and secreted from the cell. Elevated serum 3 alpha-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3 alpha-Adiol-G concentrations...

Six experiments were carried out to determine whether dihydrotestosterone (5 alpha-androstan-17 beta-ol-3-one; DHT) acts to inhibit oestradiol (OE2)-induced lordosis behaviour after its metabolic conversion to 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-androstanediol, 3 alpha-Adiol). In experiments 1 and 2, ovariectomized rats were treated with several doses of DHT or 3 alpha-Adiol, injected with OE2 and progesterone, and tested for lordosis responsiveness. Significant inhibition of lordosis occurred after a dose of 3 alpha-Adiol which was approximately threefold less than the effective DHT dose...

The present experiments were carried out to determine what physiological conditions are responsible for the acute increases in serum levels of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol, 3 alpha-Adiol) which are seen in the intact estrous female rat within 15-30 min after mating. Blood samples were obtained from proestrus rats immediately before and 20 min after injection of exogenous hormones or initiation of stress procedures, and plasma concentrations of 3 alpha-Adiol and/or progesterone (P) were measured in these samples by RIA...