PRESENCE OF IMMUNOREACTIVE CORTICOTROPIN-RELEASING HORMONE IN NORMAL AND POLYCYSTIC HUMAN OVARIES

Recently, we demonstrated the presence of immunoreactive (Ir) CRH and its receptors in the rat ovary. To determine whether CRH is also prese nt in human ovaries, we examined ovaries from normal women and patient s with the polycystic ovarian syndrome (PCOS). Immunoreactive CRH in n ormal human ovaries had a similar distribution to that of rat ovarian IrCRH, as determined by immunohistochemistry. Thus, immunoreactivity w as intense in the cytoplasm of thecal cells surrounding the ovarian fo llicles, in luteinized cells of the stroma, and in a subpopulation of cells within the corpora lutes. No IrCRH was present in oocytes of pri mordial follicles. Polycystic ovaries also had IrCRH in thecal cells; however, CRH immunostaining was less prominent or completely absent fr om the stroma or the sparsely present corpora lutes and was clearly de tected in oocytes of primordial follicles. Using a specific RIA, the I rCRH content in extracts of normal ovaries was higher than that in pol ycystic ovaries (mean +/- so, 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 +/- so, 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 o f rat/human CRH-(1-41) by reverse phase HPLC. We conclude that IrCRH i s present in normal human ovaries and follicular fluid, suggesting tha t this neuropeptide may play a regulatory role in one or more of the v arious functions of this gonad, such as ovulation and/or luteolysis, t hrough its proinflammatory properties and/or its auto/paracrine regula tion of:steroid biosynthesis, in analogy to its action on testosterone secretion by the Leydig cell. Its decreased concentration and localiz ation in primary oocytes of polycystic ovaries may he related to the i ncreased androgen biosynthesis by the theca and stroma and/or to the o ocyte dysfunction observed in women with the polycystic ovarian syndro me, respectively.