Presence of immunoreactive corticotropin-releasing hormone in normal and polycystic human ovaries.

Abstract

Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also present in human ovaries, we examined ovaries from normal women and patients with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in normal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity was intense in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutea. No IrCRH was present in oocytes of primordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent from the stroma or the sparsely present corpora lutea and was clearly detected in oocytes of primordial follicles. Using a specific RIA, the IrCRH content in extracts of normal ovaries was higher than that in polycystic ovaries (mean +/- SD, 0.075 +/- 0.02 vs. 0.038 +/- 0.009 pmol/g wet tissue, respectively; P < 0.05). Human follicular fluid samples collected from women undergoing ovarian hyperstimulation for assisted reproduction had low, but detectable, levels of IrCRH (mean +/- SD, 4.975 +/- 1.179 pmol/L), whereas IrCRH was undetectable in concurrently drawn plasma samples. IrCRH detected in normal and polycystic ovaries and in follicular fluid had similar chromatographic mobility to that of rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH is present in normal human ovaries and follicular fluid, suggesting that this neuropeptide may play a regulatory role in one or more of the various functions of this gonad, such as ovulation and/or luteolysis, through its proinflammatory properties and/or its auto/paracrine regulation of steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localization in primary oocytes of polycystic ovaries may be related to the increased androgen biosynthesis by the theca and stroma and/or to the oocyte dysfunction observed in women with the polycystic ovarian syndrome, respectively.