A variety of experiments are planned to provide insight into the mechanism by which androgens mediate testicular descent. A detailed morphologic characterization of the developing gubernaculum in the rat, mouse, and rabbit will be performed. The chemical nature of the extracellular ground substance of the mesenchymal core of the gubernaculum will be analyzed by histochemical techniques. The androgen and estrogen content of the developing gubernaculum will be assessed by specific radioimmunoassay procedures in hopes of identifying the steroid hormones that mediate gubernacular development. 5 alpha- reductase and aromatase activities will be assessed in tissue slices and in subcellular fractions of the gubernaculum throughout the period of testicular descent. Studies will be done both in vivo and in vitro to determine the effects of androgenic and estrogenic hormones on gubernacular development and testicular descent. The role of 5 alpha-dihydrotestosterone in gubernacular differentiation and development will be examined in vivo by determining the effect of prenatal exposure to 5 alpha- dihydrotestosterone on gubernacular development and testicular descent. An organ culture system will be used to examine the direct effects of androgens and estrogens on gubernacular development in vitro. The gubernacular androgen receptor will be characterized in detail. Gubernacular development and testicular descent will be investigated in two strains of mutant mice - testicular feminized and hypogonadal - in which maldescent is a uniform finding in affected offspring. Testicular descent will be investigated in the TW strain of rats with a heritable defect that causes unilateral or bilateral testicular hypoplasia. Finally, an attempt will be made to identify the androgen-dependent cell type in the gubernaculum 1) by studying the autoradiographic binding of labelled androgens and 2) by separating the cell types of the gubernaculum and studying 5 alpha-reductase activity and androgen binding in the various fractions. If homogeneous cell strains can be established from gubernacular tissues, then the effects of androgens on cell proliferation and differentiation will be examined.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Modified Research Career Development Award (K04)
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Reproductive Endocrinology Study Section (REN)
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University of Texas Sw Medical Center Dallas
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United States
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George, F W (1997) Androgen metabolism in the prostate of the finasteride-treated, adult rat: a possible explanation for the differential action of testosterone and 5 alpha-dihydrotestosterone during development of the male urogenital tract. Endocrinology 138:871-7
Bentvelsen, F M; McPhaul, M J; Wilson, C M et al. (1996) Regulation of immunoreactive androgen receptor in the adrenal gland of the adult rat. Endocrinology 137:2659-63
Bentvelsen, F M; McPhaul, M J; Wilson, J D et al. (1994) The androgen receptor of the urogenital tract of the fetal rat is regulated by androgen. Mol Cell Endocrinol 105:21-6
George, F W (1993) Postnatal expression of high rates of 5 alpha-reductase in the female rat urogenital tract. J Dev Physiol 19:187-91
Renfree, M B; Wilson, J D; Short, R V et al. (1992) Steroid hormone content of the gonads of the tammar wallaby during sexual differentiation. Biol Reprod 47:644-7
McConnell, J D; Wilson, J D; George, F W et al. (1992) Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 74:505-8
George, F W; Russell, D W; Wilson, J D (1991) Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. Proc Natl Acad Sci U S A 88:8044-7
George, F W; Matsumine, H; McPhaul, M J et al. (1990) Inheritance of the henny feathering trait in the golden Campine chicken: evidence for allelism with the gene that causes henny feathering in the Sebright bantam. J Hered 81:107-10
Lephart, E D; Peterson, K G; Noble, J F et al. (1990) The structure of cDNA clones encoding the aromatase P-450 isolated from a rat Leydig cell tumor line demonstrates differential processing of aromatase mRNA in rat ovary and a neoplastic cell line. Mol Cell Endocrinol 70:31-40
George, F W (1989) Developmental pattern of 5 alpha-reductase activity in the rat gubernaculum. Endocrinology 124:727-32

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