The epididymis is an androgen target tissue and its metabolism and epithelial secretion depend on the presence of androgens; consequently, epididymal sperm maturation does not occur in the absence of androgens. Androgen concentrations in the epididymal tissue extracts are high, especially in the caput epididymis, and caput epididymidal lumen fluid androgen concentrations are higher still. It is the long-term goal of this laboratory to understand the mechanism by which this unusual intraluminal microenvironment is maintained, to understand why such high intraluminal androgen concentrations are necessary for normal epididymal epithelial f unctions, and to understand how those androgen interact with the epididymal epithelial cells. As a result, our attention has become focused on androgen binding protein (ABP) from the testis, not for the sake of studying ABP per se, but the for the purpose of understanding the androgen microenvironment in the epididymidis and its role in epididymal epithelial function. This application proposes to investigate the little understood aspects of the endocrine physiology of the seminiferous and epididymal tubule. We will determine: (1) how the compartmentalization of androgens in the testicular and epididymal interstitium and vasculature affects the availability of those androgens to the luminal environment, 2) if movement of 3 h-androgens across the epididymal epithelium is by diffusion or if it involves membrane-associated androgen binding events, 3) if the presence of ABP or ABP bound to androgen alters nuclear localization of 3h-androgens in the caput epithelium, 4) if the presence of ABP or ABP-androgen complex in the caput epididymal lumen alters specific functions of that epididymal epithelium (protein secretion, Na+/K+ transport, or fluid reabsorption). We bring to these studies the specialized techniques of in vivo micropunture, in vivo microperifusion, and in vivo perfusion of tubules of the male reproductive tracts. These in vivo studies are important since they allow study of cell function while allowing the maintenance of normal cellular associations, intracellular architecture, and the presence of a normal extracellular matrix. This information is necessary to the understanding of 1) Sertoli cell control of an epididymal function, 2) the biological role of ABP, 3) the role of pitiutary hormones in the control of a specific Sertoli 3H-androgen movement.
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