Intracellular Signaling and function of estrogen receptors in the rat epididymis

Abstract

The epididymis connects efferent ductules to the vas deferens and functions in sperm transport, maturation, protection and storage. Although the epididymis is an androgen dependent tissue, other factors, such as estrogen may play a role in this tissue. Recent study from our laboratory has shown that the expression of estrogen receptor ESR1, mRNA and protein, is higher in the corpus than in the initial segment/caput and cauda of the epididymis, suggesting that mechanisms involved in the regulation of ESR1 in the epididymis are region-specific. ESR2 is also widely expressed throughout the epididymis and the expression of this receptor does not change in the different regions of the epididymis. Although ESR1 and ESR2 in the male reproductive tract may play a role in rapid actions of estrogen via activation of EGFR/ERK1/2, the involvement of GPER cannot be excluded. In fact, our laboratory detected the presence of GPER in testicular cells, efferent ductules and epididymis. In adult rat epididymis, the presence of mRNA for GPER was detected in all epididymal regions. The expression was higher in the corpus than in other regions of the rat epididymis. Although sperm are highly differentiated by the time they leave the testis, they are functionally immature and immotile. During their transit through the epididymis, sperm undergo biochemical changes to acquire the maturation. The maturational events are made possible by the particular luminal microenvironment created by secretory activities of the epithelial cells of the epididymis. Some of these proteins are found only in specific regions of the epididymis and their gene expression is regulated by androgens or testicular factors. In the mice epididymis, a disintegrin and metalloproteases (ADAMs) 7 and 28 are expressed in an epididimal region-specific manner and the gene expression of ADAM 7 is regulated by both androgen and testicular factors or only testicular factors regulate ADAM 28. The ADAM 7 can be transferred directly from epididymal vesicles to sperm. This protein is involved in acrosoma reaction. The estrogen plays an important role in the male reproduction system. However, the signaling pathways and the regulation of epididymal protein, for example ADAM 7 and 28, induce by estrogen and estrogen receptors in the epididymis remain to be determined. Thus, the aim of this study are to analyze: the effects of 17b-estradiol, PTT agonist of ESR1 and G-1 agonist of GPER on the expression of ERK1/2 and AKT in the initial segment/caput, corpus and cauda of the epididymis; 2. the effects of 17b-estradiol, PTT and G-1 on the expression of ADAMs 7 and 28 and the involvement of ERK1/2, AKT and EGFR on the expression of these proteins in all epididymal regions. These studies will help to explain environmental endocrine disruptor effects on male reproduction and provide new targets for the development of a male contraceptive.