Regulation of Epididymal Epithelial Cell Functions1

Abstract

It is well established that the epididymis is the site where spermatozoa are matured and stored, but our understanding of the regulation of epididymal epithelium functions and their effects on spermatozoa is still fairly limited. The most active regulator of epididymal functions seems to be dihydrotestosterone, the 5 alpha-reduced metabolite of testosterone. Our laboratory has focused on the regulation of 5 alpha-reductase, with studies encompassing its messenger RNA, protein and enzyme activity. We have also investigated the hormonal regulation and distribution of other specific key proteins found in epididymal epithelial cells that play critical roles in the function of these cells. These proteins include clusterin or sulfated glycoprotein-2 and the glutathione S-transferases (GST). Using complementary experimental approaches, including orchidectomy and hormonal replacement, efferent duct ligation, and developmental studies, we have established that 5 alpha-reductase enzyme activity is present in both nuclear and microsomal fractions; the nuclear enzyme appears almost exclusively in the initial segment of the epididymis. In addition, 5 alpha-reductase activity and the mRNAs for both the type 1 and type 2 form of the enzyme are regulated differentially with respect to age and site within the epididymis. Immunolocalization of the protein has revealed that it is located in principal cells and that its subcellular location is dependent on the region of the epididymis. These results indicate that there is both transcriptional and post-transcriptional regulation of the expression of 5 alpha-reductase. Clusterin is a hydrophobic protein secreted by Sertoli cells and found in high concentration in the epididymis. This glycoprotein is expressed at its highest levels in the initial segment and caput epididymidis and at very low levels in the corpus and cauda epididymidis of the intact rat, and it exhibits a novel pattern of androgen regulation. In the areas of highest expression, there is no androgen dependence; however, orchidectomy causes a dramatic increase in the message for clusterin, which is suppressible by androgens in the segments where expression is normally lowest. The GSTs are a family of enzymes thought to play a key role in detoxification. Members of the GST family are expressed in a region-dependent manner along the rat epididymis. We have found that the localization of one member of this enzyme family, GST P, or subunit Yp, is selective for basal cells in the corpus and cauda epididymidis.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterisation of Lyzls in mice and antibacterial properties of human LYZL6

“…27 Basal cells have been proposed to play an active role in detoxification. 28 Mouse LYZL6 expression showed principal and basal cell expression, but not all the principal and basal cells expressed LYZL. Most principal and basal cells in the corpus and cauda epididymidis expressed LYZL6 highly, with only a moderate expression in the caput, and a subset of cells expressed it in the initial segment.…”

The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis.

“…Epithelia of different parts are characterized by distinct morphologies and have different functions (Sun and Flickinger 1979;Dacheux and Paquignon 1980;Robaire and Viger 1995). Initially, the entire epididymal epithelium has a homogeneous appearance.…”

Ultrastructure of the epithelium lining of cauda epididymidis in mongrel dogs

“…The epithelium lining of the epididymis of mammals, because of its role in providing a suitable milieu for the maturation of spermatozoa, has been the object of numerous cytological and histochemical investigations (Robaire & Hermo 1988, Robaire & Viger 1995, Schimming & Vicentini 2005, Lorenzana et al 2007, Alkafafy et al 2012.…”