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Localization and Secretion of Inhibin/Activin Subunits in the Human and Subhuman Primate Fetal Gonads^*

Reproductive Endocrinology Center, University of California San Francisco, San Francisco, California 94143
Clayton Laboratories for Peptide Biology, The Salk Institute LaJolla, California 92037

Address all correspondence and requests for reprints to: Robert B. Jaffe, M.D., Reproductive Endocrinology Center, M-1490, Box 0132, University of California, San Francisco, San Francisco, California 94143.

Little is known about the ability of the fetal primate gonads to produce inhibin/activin. We investigated the presence of the -, β_A-, and β_B-subunits of inhibin/activin in fetal human (16–23 weeks gestational age) and rhesus monkey (days 150–157 of gestation; term = 165 days) testes and ovaries by immunocytochemistry. The regulation of -inhibin secretion by gonadotropins was studied in fetal testicular cultures. In the human fetal testis, -subunit immunostaining was found in interstitial and intratubular cells, while β_A- and β_B-subunit immunostaining occurred in clusters of Leydig cells that were clearly demarcated from groups of Leydig cells that were immunonegative. In the late gestational monkey testis, the asubunit was localized in tubular cells, and the β_B-subunit was present in the tubules and interstitium. Testicular cells from midgestation human testes secreted detectable immunoreactive -inhibin in response to FSH and hCG stimulation; -inhibin levels were significantly higher after hCG than FSH. In contrast, levels of -inhibin secreted by rhesus monkey testicular cells were significantly increased by FSH, but not hCG.

In the ovary, only weak β_B-subunit immunoreactivity was detected in granulosa cells of a few primary follicles from midgestational human fetal ovaries. In contrast, all three subunits were found in granulosa cells of numerous primary and secondary follicles in the late gestation rhesus monkey ovary. In light of recent evidence that inhibins/activins have actions on gonadal differentiation and growth modulation in vitro, as well as endocrine effects on the fetal pituitary, we propose that these proteins may have intragonadal and endocrine roles in human and subhuman intrauterine gonadal development.

^* Presented in part at the 72nd Annual Meeting of The Endocrine Society, Atlanta, GA, 1990. This work was supported in part by NIH Grants HD-18726 and P30–11729 and by Fogarty Scholarship TW04258–01 (to J.R.).

Received July 16, 1990.

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