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.
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