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Expression and enzymatic activity of the P450c17 gene in human adipose tissue
Cristina Puche1, Marta José, Albert Cabero
1Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospitals Vall d'Hebron, Barcelona, Spain.
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 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-HSD have been 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 17alpha-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 17alpha-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 17alpha-hydroxylase activity in adipose tissue, together with previously reported enzymatic activities such as 3beta-HSD and17beta-HSD, might suggest a local production of androgens in this tissue.