Granulosa Cell Desensitization: Effects of Gonadotropins on Antral and Preantral Follicles*

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Abstract
The present studies examine the time course, hormonal specificity, and reversibility of gonadotropin-induced desensitization in rat granulosa cells in vivo and relate these events to changes in FSH and LH/hCG receptor availability. To these ends, desensitization to gonadotropins was compared in granulosa cells of preantral and antral follicles. Granulosa cells from antral follicles of estradiol- and FSH-primed hypophysectomized rats possess receptors for both FSH and LH/hCG. These cells appeared to exhibit heterologous desensitization of gonadotropin-stimulated cAMP accumulation in vivo; refractoriness initiated by either gonadotropin (5 μg human FSH or 5–50 IU hCG, administered iv) was communicated to both gonadotropin/adenylate cyclase response systems and prevented a secondary hormone-stimulated increase in cAMP accumulation. Heterologous desensitization was demonstrable within 120 min and occurred in the absence of detectable changes in the binding of 125I-labeled heterologous hormone to isolated granulosa cells. In contrast, granulosa cells in preantral follicles of estradioltreated rats contain FSH but not LH/hCG receptors; these cells exhibited desensitization to FSH but not to hCG within 120 min of acute administration of 1 or 5 μg human FSH. The cAMP accumulation that was observed in response to hCG in these estradiol-treated rats appeared to originate from theca and interstitial compartments and was found in the fluid accompanying granulosa cells during their removal from the ovary. Recovery of FSH-stimulated cAMP accumulation was demonstrable by 24–48 h. Acute administration of human FSH to estradiol-primed rats did not prevent subsequent induction of LH/hCG receptor by FSH given sc. Thus, desensitization to FSH in preantral follicles of estradiol-treated rats was rapid, homologous, and apparently reversible in vivo, since it did not prevent at least one functional response to FSH. The present results suggest that heterologous desensitization to gonadotropins requires the coexistence of receptors for both FSH and LH/hCG on the same granulosa cells and that these receptors may share a common mechanism of coupling to adenylate cyclase. (Endocrinology106: 1786, 1980)

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