Endocrine Abstracts (2002) 3 OC38

Autocrine generation of androgens within adipose tissue: Implications for polycystic ovarian syndrome (PCOS)

B Sinha, JW Tomlinson, IJ Bujalska, M Hewison & PM Stewart

Division of Medical Sciences, University of Birmingham, Birmingham, UK.

The most robust biochemical marker for the diagnosis of PCOS is hyperandrogenism (androstenedione, testosterone), thought to originate from the ovaries and/or adrenals. However the change in circulating androgen/LH ratios with increasing body mass in women with PCOS suggests the autocrine generation of androgens within adipose tissue itself. The enzyme 17beta hydroxysteroid dehydrogenase (17betaHSD) which has seven human isoforms is an important regulator of sex steroid metabolism. This enzyme converts inactive androstenedione (A) to active testosterone (T) and is also involved in the interconversion of Oestradiol (E2) and Oestrone (E1).

Paired omental (om) and subcutaneous (sc) fat biopsies were obtained from 16 healthy women undergoing elective abdominal surgery.

17betaHSD expression in whole tissue and cultured pre-adipocytes were assessed using reverse transcriptase polymerase chain reaction (RT-PCR). Additionally, specific enzyme assays were performed on cultured pre-adipocytes. In cultured preadipocytes aromatase activity was not significantly different (sc 36.7 +/- 12.5 pmol/mgprotein/hr [mean +/- SE] vs. om 29.7 +/- 6.9). Conversion of E1 to E2 was higher in subcutaneous tissue (34.1 +/- 9.8 vs. 19.3 +/- 9.4 p=0.08). Conversion of A to T was similar in omental and subcutaneous tissues (17.6 +/- 5.8 vs. 18.4 +/- 5.4). RT- PCR on mRNA extracted from cultured preadipocytes showed a higher expression of type 2 and type 5 isoenzymes of 17betaHSD in subcutaneous when compared to matched omental tissue. However RT-PCR on whole tissue shows that only subcutaneous not omental fat expresses the type 5 isoenzyme of 17betaHSD responsible for the conversion of A to T.

In conclusion, it appears that subcutaneous fat acts as an intracrine organ leading to the formation of androgens and this may contribute to the hyperandrogenism seen in some patients with obesity.

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