Cellular and Animal Studies: Insights into Pathophysiology and Therapy of PCOS

Adipose Tissue is a Potential Source of Hyperandrogenism in Obese Female Rats

“…To support these findings, we measured steroidogenic gene expression levels in adipose tissue and found prominent gene expression levels of all tested steroidogenic enzyme genes in both depots and in young and adult female rats. These observations are also in line with recent findings by others including adipose tissue in rats and humans . Blouin et al also found higher expression in subcutaneous compared with omental fat for AKR1C2, AKR1C3 , and Hsd3b1 ; for the steroid sulfatase; and for the androgen receptor .…”

“…Ovaries and adrenal glands are considered to be the major contributors to circulating androgens and are both likely to cause androgen excess in PCOS . Studies suggest that the ovary is the main source of androgen excess .…”

“…More novel studies suggest that besides the adrenal glands and ovaries, other sites, including adipose tissue, hair follicles, and genital skin, also contribute to androgen biosynthesis and circulating androgens . Human adipose tissues express hydroxy‐delta‐5‐steroid dehydrogenase ( HSD3B2 ), hydroxysteroid 17‐beta dehydrogenase 3 ( HSD17B3 ), and steroid 5 alpha‐reductase 2 ( SRD5A2 ) and are thus capable of converting circulating plasma dehydroepiandrosterone sulfate, dehydroepiandrosterone (DHEA), androstenedione, and testosterone to more potent forms of androgens .…”

“…Recent findings further suggest that the presence of steroidogenic acute regulatory protein ( StAR ) and cytochrome P450 family 11 subfamily A member 1 ( CYP11A1 ) may facilitate de novo steroidogenesis from cholesterol in adipose tissues . Indran et al estimated that 25% of testosterone in females is produced by the ovaries, that 25% is produced by the adrenals, and that a total of 50% is produced by peripheral tissues, including adipose tissue . This addresses the importance of investigating the role of adipose tissue in steroid production and storage to better understand the mechanisms of hyperandrogenism in the search for better therapeutic options.…”

Polycystic Ovarian Syndrome and Hirsutism

“…Furthermore increased expression of DENND1A variant 2 was detected in the theca cells taken from women with PCOS. Moreover, over expression of DENN 1A variant 2 in normal theca cells resulted in a PCOS phenotype with increased androgen production (14). Recent breakthroughs have demonstrated that dietary medium -chain fatty acid decanoic acid can restore estrous cyclicity and lower androgen levels in an animal model of PCOS (14).…”