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Title: Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

Abstract

In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. Themore » term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.« less

Authors:
;
Publication Date:
Research Org.:
Univ. of Southern California School of Medicine, Los Angeles
OSTI Identifier:
5964611
Resource Type:
Journal Article
Resource Relation:
Journal Name: Fert. Steril.; (United States); Journal Volume: 43:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; OXIDOREDUCTASES; ENZYME ACTIVITY; SKIN; SAMPLING; SKIN DISEASES; ETIOLOGY; ANDROGENS; ANDROSTANES; CARBON 14 COMPOUNDS; ENDOCRINE DISEASES; ESTRADIOL; FEMALE GENITALS; HAIR; IN VITRO; PATIENTS; TESTOSTERONE; TRACER TECHNIQUES; WOMEN; ANIMALS; BODY; DISEASES; ENZYMES; ESTRANES; ESTROGENS; FEMALES; HORMONES; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; KETONES; LABELLED COMPOUNDS; MAMMALS; MAN; ORGANIC COMPOUNDS; ORGANS; PRIMATES; STEROID HORMONES; STEROIDS; VERTEBRATES; 551001* - Physiological Systems- Tracer Techniques

Citation Formats

Serafini, P., and Lobo, R.A. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism. United States: N. p., 1985. Web.
Serafini, P., & Lobo, R.A. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism. United States.
Serafini, P., and Lobo, R.A. 1985. "Increased 5. cap alpha. -reductase activity in idiopathic hirsutism". United States. doi:.
@article{osti_5964611,
title = {Increased 5. cap alpha. -reductase activity in idiopathic hirsutism},
author = {Serafini, P. and Lobo, R.A.},
abstractNote = {In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.},
doi = {},
journal = {Fert. Steril.; (United States)},
number = ,
volume = 43:1,
place = {United States},
year = 1985,
month = 1
}
  • We measured the 5 ..cap alpha..-reductase activity in isolated cell preparations of rat adipose tissue using the formation of (/sup 3/H) dihydrotestosterone from (/sup 3/H) testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5..cap alpha..-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity thanmore » those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10/sup -8/ M), when added to the medium, caused a 90% decrease in 5..cap alpha..-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5..cap alpha..-reductase activity in each tissue studied.« less
  • To elucidate the phenotypic expression of proliferating prostatic cells, rats were castrated, and the regenerating process of involuted ventral prostates during testosterone propionate (TP) administration was investigated by examining morphology, (5-{sup 125}I)iododeoxyuridine ({sup 125}I-UdR) uptake, DNA content, weight, acid phosphatase, and delta 4-steroid 5 alpha-reductase (5 alpha-reductase) activities. Morphologically, TP treatment initially increased the number of epithelial cells lining glandular lobules and subsequently restored the shape of epithelial cells. {sup 125}I-UdR uptake peaked on Day 3 of TP treatment and stayed at higher levels than for uncastrated controls until Day 14 of treatment. Prostatic weight, protein content, acid phosphatase, andmore » DNA content returned to uncastrated control levels by Day 14 of TP treatment. TP administration markedly stimulated prostatic 5 alpha-reductase activity, which peaked on the Day 5 of treatment and decreased to uncastrated control levels by Day 14 of treatment. It is concluded that TP administration to castrated rats initially induced active mitotic division of the remaining stem cells, followed by formation of differentiated functional epithelial cells. Prostatic 5 alpha-reductase was highly active at the initial phase of active mitotic cell division. The major portion of the increased enzyme activity can be regarded as a phenotypic expression of stem or transient cells of prostatic epithelium.« less
  • The molecular basis of 5{alpha}-reductase (5{alpha}R) deficiency was investigated in four patients from three European families. In the French family, the first patient was raised as a female, and gonadectomy was performed before puberty. The second sibling, also raised as female, differed in that gonadal removal was performed after the onset of pubertal masculinization. The other two patients, both from Polish families, developed masculinization of external genitalia during puberty. All patients developed a female sexual identity. In all cases, no known consanguinity or family history of 5{alpha}R deficiency was reported. The genomic DNAs of the patients were sequenced after polymerasemore » chain reaction amplification of the five exons of the 5{alpha}R type 2 gene. We found two homozygous mutations responsible for gutamine to arginine and histidine to arginine substitution in families 1 and 3, respectively. In family 2, we found a heterozygous mutation responsible for an asparagine to serine substitution at position 193. The glutamine/arginine 126 mutation in the French family was previously reported in a Creole ethnic group, and the Polish histidine/arginine 231 mutation was previously reported in a patient from Chicago, Moreover, all of the mutations created new restriction sites, which were used to determine the kindred carrier status in the three families. Because 5{alpha}R deficiency is known to be heterogenous disease in terms of clinical and biochemical expression, our data suggest that molecular biology analysis of the type 2 gene could be an essential step in diagnosing 5{alpha}R deficiency. 22 refs., 3 figs., 1 tab.« less
  • Catalysts and Chemicals Inc. demonstrated that the methanation activity of a catalyst increases with increased nickel content and decreases with increased particle size and that an increase in the steam/gas ratio of the feed gas tends to increase carbon monoxide conversion but does not affect the methanation rate. These findings are based on a laboratory investigation of over 40 catalysts to determine the optimum catalyst for the methanation of synthesis gas from coal and to develop an applicable kinetic system. The investigation involved determination of the necessary catalyst loading design operating conditions, effect of particle size, effect of various tracemore » constituents (H/sub 2/S, HCl, NO/sub x/, methanol, ethane, ethylene, propane, propylene, and benzene) on catalyst performance, and resistance of the catalyst to various steam/gas ratios. The report includes a complete bibliography of the literature search on reported developments and kinetics which were used to develop the kinetic system.« less