The long-term objective of this research is to provide a means for contraception by blocking development or maintenance of sperm fertilizing ability in the epididymis. A working model for regulation of epididymal function was developed, and one of it's features is """"""""sparing"""""""" of androgen binding protein (ABP) while most bulk protein is removed in the proximal excurrent duct system. It is hypothesized that regulatory molecules (ranging from ions to specific proteins or steroids) produced in nearby or upstream cells control functions in 5 zones within the epididymis. Consequently, the specific aims are: (1) establish the dynamics of androgen binding protein (ABP) secretion and/or uptake and recycling in the excurrent ducts, and determine if there are receptors for ABP in the epididymis, and (2) Determine if upstream-to-downstream signaling by molecules in luminal fluid alters function of the epididymal epithelium, and the nature of changes induced by deprivation of such signals. Six major studies or experiments are outlined. Studies the first 2.5 yr will focus on the ABP system, and it should be considered as a model for retention and use of other trace solutes of testicular or epididymal origin. In vivo studies will combine micropuncture, molecular biology and electron microscopy to study secretion and endocytosis of ABP, and the composition of luminal fluids. In vitro studies will focus on quantification and characterization of the postulated ABP receptor. During the last 1.5 yr, segments of the epididymal duct in rams will be isolated by microsurgery to establish dependence of the epithelium on upstream inputs. The profile of secreted proteins and epithelial morphology will serve as endpoints to monitor epithelial function 10 and 25 days after elimination of luminal regulatory factors. Cultured principal cells from the cauda and caput epididymidis will be used to determine if a factor(s) in luminal fluid entering the cauda supports epithelial function in terms of 5alpha-reductase activity.
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