Inhibin, a glycoprotein synthesized by the Sertoli cells of the seminiferous epithelium of the testis, is involved in regulating pituitary gonadotropin secretion, and possibly involved in intragonadal regulation as well. We propose to develop a non-human primate model, using i) testes tissue from monkeys of various stages of sexual development and ii) hormonally-stimulated, primary Sertoli cell-enriched cultures from prepubertal monkeys, to characterize the regulation of steady state levels of messenger ribonucleic acid (mRNA) for the subunits of inhibin. The inhibin mRNA values will also be compared with the mRNA levels for another Sertoli cell secreted protein, Androgen-Binding protein (ABP). This comparison will allow a wider perspective to be achieved with respect to hormonally-regulated genes in the primate Sertoli cell. Complementary RNA (cRNA) probes to i) human sex hormone-binding globulin (SHBG), a protein closely related to ABP, and ii) the alpha, beta A, and beta B-subunits of inhibin, will be used in hybridization assays to quantitate the mRNA levels for these proteins in testes tissue and in cultured cells. mRNA levels for the inhibin subunits, as well as ABP, will be measured in five developmental stages of sexual maturation. These mRNA values will then be compared with the concentration of inhibin in the testes, determined by bioassay and/or radioimmunoassay (RIA). We will also determine whether there is any correlation of these values with the endogenous levels of androgen and gonadotropin in the serum and/or testes. The ABP and inhibin subunit mRNA's will also be measured by in situ hybridization in testicular cross-sections during sexual maturation as well as during the various stages of the spermatogenic cycle in adult animals. The effect of FSH, EGF, androgen, as well as other factors, on the expression of the inhibin subunit genes in cultured Sertoli cells will also be examined. This will enable us to further elucidate the hormonal regulation of inhibin at a molecular level. The information learned from primate Sertoli cell function, with respect to the hormonal regulation of inhibin gene expression, may also be valuable for the understanding of human physiology, since these experiments are usually not possible or practical in the human. A major advantage of using serum and testes, obtained during orchiectomy is that no monkeys are killed specifically for these studies. The study of primate inhibin may also lead to a greater understanding of fertility and infertility in the human.
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