A Gonadotropin-Releasing Hormone (GnRH)-Like Protein in Human Ovaries: Similarity to the GnRH-Like Ovarian Protein of the Rat*

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Abstract
The rat ovary contains significant amounts of a GnRH-like protein, but does not contain readily detectable GnRH. We, therefore, determined whether human ovaries contain a similar GnRH-like protein. Extracts of human ovaries as well as rat ovaries, rat hypothalami, and rat plasma were examined for their content of both GnRH-like protein and GnRH. GnRH-like activity was detected by inhibition of binding of GnRH to rat ovarian membrane receptors [radioreceptor assay (RRA)]. GnRH was detected with a specific GnRH RIA. Equivalent amounts of GnRH-like activity were found in both human and rat ovaries, whereas GnRH was not detected. The human and rat ovarian GnRH-like materials had identical retention times after reverse phase high pressure liquid chromatography, and these were clearly different from that of authentic GnRH. Furthermore, the ovarian GnRH-like activity was clearly separated by HPLC from GnRH and GnRH-like activities extracted from rat hypothalami. Plasma contained neither GnRH-like nor GnRH activity. The ovarian GnRH-like activity was protease and heat sensitive, whereas hypothalamic GnRH and GnRH-like activity were protease sensitive, but not heat sensitive. The ovarian GnRH-like protein did not inhibit the specific binding of prostaglandin F2α to rat ovarian membranes under conditions of assay similar to the GnRH RRA. The ovarian GnRH-like protein did not have GnRH peptidase activity, its inhibition of GnRH binding in the RRA was reversible, and bacitracin (protease inhibitor) had no effect on assay of the ovarian GnRH-like protein by RRA. We conclude that the human ovary contains a GnRH-like protein similar, if not identical, to the GnRH-like protein of the rat ovary, which is different from GnRH and the GnRH-like protein of the hypothalamus. The presence of the same GnRH-like material in human and rat ovary raises the possibility tha t this protein may mediate responses in the human ovary similar to the antigonadotropic actions of GnRH in the rat ovary.