Expression and enzymatic activity of the P450c17 gene in human adipose tissue

Objective: P450 aromatase activity increases with age in adipose tissue. Increased oestrogen production has also been observed in obese elderly women, and has been related to the pathogenesis of endometrial cancer. Since peripheral oestrogen production requires the presence of androgenic metabolites, and a recent report from our laboratory showed very low expression levels of P450c17 mRNA in most postmenopausal ovaries analysed, we hypothesised on the existence of an alternative source of androgens Since steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD have heen described in adipose tissue of primates and humans respectively, we aimed to analyse the possible expression of the P450c17 gene in adipose tissue, and its enzymatic capability. Design: A prospective non-randomised clinical research study. Methods: Subcutaneous abdominal adipose tissue and random pieces of whole normal ovaries were collected at surgery from nineteen women undergoing bilateral oophorectomy for non-ovarian gynaecological disease. P450c17 mRNA expression levels were measured by RT-PCR/Southern blot analysis, and 17α-hydroxylase enzymatic activity in dispersed cell homogenates was performed by thin-layer chromatography, using 14 C-progesterone as a substrate. Results: The study provides the first description of 17α-hydroxylase activity in adipose tissue and the detection of a new form of the P450c17 cDNA containing a 156 bp in-frame deletion in the first exon. Conclusions: The description of 17α-hydroxylase activity in adipose tissue, together with previously reported enzymatic activities such as 3β-HSD and 17β-HSD, might suggest a local production of androgens in this tissue.