This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McTernan, P. G. Articles by Kumar, S. Search for Related Content PubMed PubMed Citation Articles by McTernan, P. G. Articles by Kumar, S.

Glucocorticoid Regulation of P450 Aromatase Activity in Human Adipose Tissue: Gender and Site Differences

Division of Medical Sciences (P.G.M., L.A.A., A.J.A., M.C.E., A.H.B., P.M.S., S.K.), University of Birmingham, Birmingham B15 2TH; and Cellular Pathology (J.C.) and Department of Medicine (A.H.B., S.K.), Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom

Address all correspondence and requests for reprints to: Dr. P. G. M^cTernan, Division of Medical Sciences, Department of Medicine, Clinical Research Block, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom. E-mail: . p.g.mcternan.20{at}bham.ac.uk

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 [1ß-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.

This article has been cited by other articles:

				K. Blouin, M. Nadeau, J. Mailloux, M. Daris, S. Lebel, V. Luu-The, and A. Tchernof Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis Am J Physiol Endocrinol Metab, February 1, 2009; 296(2): E244 - E255. [Abstract] [Full Text] [PDF]

				F. Moreau, H. Mittre, A. Benhaim, C. Bois, J. Bertherat, S. Carreau, and Y. Reznik Aromatase expression in the normal human adult adrenal and in adrenocortical tumors: biochemical, immunohistochemical, and molecular studies Eur. J. Endocrinol., January 1, 2009; 160(1): 93 - 99. [Abstract] [Full Text] [PDF]

				D. P. Rose, S. M. Haffner, and J. Baillargeon Adiposity, the Metabolic Syndrome, and Breast Cancer in African-American and White American Women Endocr. Rev., December 1, 2007; 28(7): 763 - 777. [Abstract] [Full Text] [PDF]

				M. Tanaka, R. Koga, H. Tsuda, K. Imai, S. Abe, T. Masuda, M. Iwamoto, E. Nakazono, T. Kamohara, N. Kinukawa, et al. Subcutaneous Fat Accumulation Shows a Beneficial Correlation with Serum Cholesterol in Postmenopausal Japanese Women Experimental Biology and Medicine, September 1, 2007; 232(8): 1064 - 1070. [Abstract] [Full Text] [PDF]

				W. de Ronde, Y. T. van der Schouw, M. Muller, D. E. Grobbee, L. J. G. Gooren, H. A. P. Pols, and F. H. de Jong Associations of Sex-Hormone-Binding Globulin (SHBG) with Non-SHBG-Bound Levels of Testosterone and Estradiol in Independently Living Men J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 157 - 162. [Abstract] [Full Text] [PDF]

				S. Rodriguez-Cuenca, M. Monjo, A. M. Proenza, and P. Roca Depot differences in steroid receptor expression in adipose tissue: possible role of the local steroid milieu Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E200 - E207. [Abstract] [Full Text] [PDF]

				M. N. Dieudonne, M. C. Leneveu, Y. Giudicelli, and R. Pecquery Evidence for functional estrogen receptors {alpha} and {beta} in human adipose cells: regional specificities and regulation by estrogens Am J Physiol Cell Physiol, March 1, 2004; 286(3): C655 - C661. [Abstract] [Full Text] [PDF]

				M. Zinger, M. McFarland, and N. Ben-Jonathan Prolactin Expression and Secretion by Human Breast Glandular and Adipose Tissue Explants J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 689 - 696. [Abstract] [Full Text] [PDF]