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The effect of obesity on the ratio of type 3 17β-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women

International Journal of Obesity volume 26, pages 165–175 (2002)Cite this article

Abstract

OBJECTIVES: To investigate (1) whether type 3 17β-hydroxysteroid dehydrogenase (17β-HSD), the enzyme which catalyzes the conversion of androstenedione to testosterone in the testis, is co-expressed with P450aromatase in the preadipocytes of women, and (2) whether the relative expression of type 3 17β-HSD and aromatase varies in subcutaneous abdominal vs intra-abdominal adipose tissue of women.

SUBJECTS: Subcutaneous abdominal and intra-abdominal adipose tissue was obtained from women undergoing elective abdominal surgery (age 22–78 y, body mass index (BMI) 22.4–52.9 kg/m2).

MEASUREMENTS: Expression of type 3 17β-HSD in adipose cell fractions was determined using RT-PCR. Preadipocyte steroidogenesis was investigated in primary cultures using androstenedione as substrate. Messenger RNA levels for type 3 17β-HSD and aromatase were measured in adipose tissue from the subcutaneous abdominal and intra-abdominal depots using a quantitative multiplex competitive RT-PCR assay.

RESULTS: Type 3 17β-HSD is co-expressed with aromatase in the abdominal preadipocytes of women. Cultured preadipocytes from both subcutaneous abdominal (n=5) and intra-abdominal (n=5) sites converted androstenedione to testosterone, and there was minimal conversion of androstenedione to estrone. Consistent with this, the levels of type 3 17β-HSD mRNA were significantly higher than aromatase mRNA at both sites (P<0.05; n=8 subcutaneous abdominal, n=12 intra-abdominal adipose tissue). The ratio of levels of 17β-HSD mRNA to aromatase mRNA in intra-abdominal adipose tissue was positively correlated with BMI (n=11, r=0.61, P<0.05) and waist circumference (n=10, r=0.65, P<0.05). The converse was found in subcutaneous abdominal adipose tissue.

CONCLUSION: The intra-abdominal adipose tissue of women may be substantially androgenic, increasingly so with increasing obesity, particularly central obesity. While androgen production by this adipose tissue deposit may not contribute to circulating testosterone levels due to hepatic clearance, it may have hitherto unrecognised local effects in the intra-abdominal adipose tissue and also on the liver via the hepatic portal system. These studies suggest a mechanism linking central obesity with insulin resistance and dyslipidaemia.

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Acknowledgements

The type 3 17β-HSD cDNA was the gift of Dr S Andersson, the Cecil H and Ida Green Center for Reproductive Biological Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. The aromatase cDNA was kindly provided by Professor E Simpson, Prince Henry's Institute of Medical Research, Victoria, Australia. The authors wish to thank the surgeons of Flinders Medical Centre, especially Associate Professor D Wattchow, for collection of the adipose tissue samples. We also thank Drs B Mojarrabi, R Bhasker and D Male for invaluable technical advice, and Ms W King for her assistance with preparation of the manuscript.

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  1. AM Corbould

    Present address: Division of Women's Health, Brigham and Women's Hospital, 75 Francis Street, Boston, 02115, MA, USA

  2. MJ Bawden

    Present address: Department of Microbiology and Immunology, University of Adelaide, 5000, South Australia, Australia

Authors and Affiliations

  1. Department of Medicine, Flinders University of South Australia, Bedford Park, South Australia, Australia

    AM Corbould, MJ Bawden, TC Lavranos, RJ Rodgers & SJ Judd

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Correspondence to AM Corbould.

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Corbould, A., Bawden, M., Lavranos, T. et al. The effect of obesity on the ratio of type 3 17β-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women. Int J Obes 26, 165–175 (2002). https://doi.org/10.1038/sj.ijo.0801886

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