Localization and secretion of inhibin/activin subunits in the human and subhuman primate fetal gonads

Little is known about the ability of the fetal primate gonads to produce inhibin/activin. We investigated the presence of the α-, 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 α-inhibin secretion by gonadotropins was studied in fetal testicular cultures. In the human fetal testis, α-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 α-subunit 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 α-inhibin in response to FSH and hCG stimulation; α-inhibin levels were significantly higher after hCG than FSH. In contrast, levels of α-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.