McTernan, P. G. (Philip G.), Anderson, Leah A., Anwar, Aresh J., Eggo, Margaret C., Crocker, John, Barnett, Anthony H., Stewart, Paul M. and Kumar, Sudhesh (2002) Glucocorticoid regulation of P450 aromatase activity in human adipose tissue : gender and site differences. Journal of Clinical Endocrinology and Metabolism, Volume 4 (Number 3 ). pp. 209-213. doi:10.1210/jc.87.3.1327

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Abstract

The distinct gender-specific patterns of fat distribution in men and women (android and gynoid) suggest a role for sex steroids. In keeping with these observations, it has been suggested that estrogens can promote preadipocyte cell proliferation and/or differentiation. The enzyme aromatase P450 is responsible for the conversion of androgen precursor steroids to estrogens and may, therefore, have a role in regulating adipose tissue mass and its distribution. We have investigated the glucocorticoid regulation of aromatase expression in human adipose tissue, specifically to define any site- and gender-specific differences. Abdominal subcutaneous (Sc) and omental (Om) adipose tissue was obtained from male and female patients undergoing elective surgery. After collagenase digestion, preadipocytes were cultured in serum-free medium, for 6–10 d, until confluent with either cortisol (10−6 m, 10−7 m) or insulin (500 nm) or a combination of both treatments. Adipocytes were studied in suspension cultures. Aromatase activity was assessed using tritiated [1β-3H]-androstenedione as substrate. In Sc preadipocytes, basal aromatase activity increased in females from 11.5 ± 1.4 (mean ± sem) to 28.0 ± 1.8 pmol/mg·h (n = 17, P < 0.05) with 10−6 m cortisol. By contrast, in males, aromatase activity was inhibited by 10−6 m cortisol (19.4 ± 2.4 pmol/mg·h vs. 7.5 ± 1.3, n = 9, P < 0.01; men vs. women, P < 0.005). These data were endorsed through Western blot analysis using an in-house antihuman aromatase antibody, which recognized a specific 55-kDa species. Aromatase activity was less at Om sites in preadipocytes, increasing in females from 1.1 ± 0.2 to 3.2 ± 0.7 pmol/mg·h with 10−6 m cortisol (P < 0.05) and in males from 2.6 ± 0.1 pmol/mg·h to 7.8 ± 0.3 pmol/mg·h after cortisol (men vs. women, P < 0.001). Cortisol-induced aromatase activity in Om adipocytes from postmenopausal females was higher than that in premenopausal females (P < 0.001). Insulin had no independent effect on aromatase expression, but coincubation of preadipocytes with cortisol and insulin eliminated both gender- and site-specific differences. In conclusion, in women, but not men, cortisol increased aromatase activity at Sc sites, and this may facilitate predilection for Sc adiposity in females. The observed site-, gender-, and menopausal-specific differences in the glucocorticoid regulation of this enzyme may contribute to the gender- and menopausal-specific patterns of fat distribution.

Item Type:	Journal Article
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Journal of Clinical Endocrinology and Metabolism
Publisher:	The Endocrine Society
ISSN:	0021-972X
Official Date:	2002
Dates:	Date Event 2002 Published
Volume:	Volume 4
Number:	Number 3
Page Range:	pp. 209-213
DOI:	10.1210/jc.87.3.1327
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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