Androgen generation in adipose tissue from women with simple obesity – a site-specific role for 17β-hydroxysteroid dehydrogenase type 5

Women with PCOS have high circulating androgens, thought to originate from ovaries and adrenals. In addition, PCOS patients frequently suffer from the metabolic syndrome including obesity. However, serum androgens are positively associated with body mass index (BMI) not only in PCOS, but also in simple obesity. This suggests androgen synthesis within adipose tissue. Thus we investigated androgen generation in human adipose tissue, including expression of 17β-hydroxysteroid dehydrogenase (17βHSD) isozymes, important regulators of sex steroid metabolism, e.g. converting androstenedione (A) to testosterone (T). Paired omental (om) and subcutaneous (sc) fat biopsies were obtained from 27 healthy women undergoing elective abdominal surgery (age range 30–50yrs, BMI 19.7–39.2kg/m²). Preadipocyte monolayer cultures from sc and om fat were incubated with 40 nM A containing radiolabeled tracer. Steroids were separated and identified by TLC, revealing efficient conversion of A to T in both sc and om fat. RT-PCR of whole fat and preadipocytes of sc and om origin showed expression of 17βHSD4, ample expression of 17βHSD5, but no expression of 17βHSD isozymes 1, 2, or 3. cDNA microarray analysis confirmed this expression pattern (17βHSD5>>17βHSD4) and suggested a higher expression of 17βHSD5 in sc than in om fat. Accordingly, quantitative realtime RT-PCR showed significantly higher expression of 17βHSD5 in sc fat (p<0.05), with significantly higher expression in whole fat then in preadipocytes (p<0.01). BMI significantly correlated with 17βHSD5 expression in sc whole fat (p<0.05) suggesting an involvement of 17βHSD5 in adipocyte differentiation. This was further supported by a significant increase in 17βHSD5 expression following differentiation of sc preadipocytes to mature adipocytes (p<0.05). In conclusion, human fat is capable of active androgen synthesis catalyzed by 17βHSD5, which may also be an important site-specific modulator of adipocyte differentiation.