Regulation of the initial segment of the murine epididymis by dihydrotestosterone and testicular exocrine secretions studied by expression of specific proteins and gene expression

Abstract

The murine caput epididymidis responded to deprivation of luminal fluid from the testis by regression of the initial segment but maintenance of the adjacent proximal and distal caput regions, as judged by immunohistochemical staining of the glutamate transporter EAAC1 and the lipocalin MEP17 and enzymatic activity of beta-galactosidase (beta-Gal). Additional removal of circulating androgens by bilateral castration similarly led to loss of the initial segment and of the proximal caput but the distal caput was transformed into an epithelium containing more apical than principal cells staining for EAAC1; this epithelium resembled the precursor epithelium usually only seen in prepubertal juveniles. Administration of dihydrotestosterone (DHT) to the castrates maintained the proximal and distal caput epithelia and induced a proximal epithelium, which resembled the initial segment in its prominent staining for Golgi, EAAC1 and beta-Gal activity, although it was short and exhibited no MEP17 expression. DHT was present in the c-ros knockout caput epididymidis lacking the initial segment and in the heterozygous organ but the DHT concentration was lower in the knockout corpus. The maintenance of the full complement of epithelia in the murine caput epididymidis in the adult thus requires a combination of luminal fluid from the testis, tissue DHT and the presence of the c-ros oncogene.

Androgen Receptor Expression in the Caput Epididymal Epithelium Is Essential for Development of the Initial Segment and Epididymal Spermatozoa Transit

“…Endocrinology, February 2011, 152(2):718 -729 endo.endojournals.org 725 of androgens after orchidectomy results in regression of segment I and dedifferentiation of segments II and III to a 'precursor' state, suggesting that continuous androgen exposure is required to maintain a differentiated epididymal epithelium (16). Consistent with this, we conclude that in the absence of epithelial AR, the proximal epithelium of the caput is unable to undergo correct terminal differentiation, resulting in complete failure of development of the IS.…”

“…At postnatal ages, acute withdrawal of androgens after orchidectomy results in apoptosis of epididymal epithelial principal cells (14,15) and dedifferentiation of the caput epididymal epithelium to a 'precursor' state (16), demonstrating that androgens are important for maintenance of epithelial cell identity. However, whether this impact of testosterone withdrawal is due to direct action on the epithelial cells or indirect action via the stromal cells remains unclear, as both cell types express AR.…”

Targeted Inactivation of the Androgen Receptor Gene in Murine Proximal Epididymis Causes Epithelial Hypotrophy and Obstructive Azoospermia

“…Whereas this model may apply to the rat, the situation in the mouse appears to be somewhat different. Although the administration of DHT after orchidectomy can restore the morphology of murine IS to some extent (22), the genital structures and fertility of males with 5α-reductase type I knockout (23), and combined type I and II knockout (24), are largely uncompromised, with the exception of smaller prostates and seminal vesicles. The urogenital tissues (prostate, seminal vesicles, coagulating glands) of the double-knockout mice were found to accumulate high levels of testosterone, indicating that conversion of testosterone to DHT largely functions as signal amplification mechanism and is redundant in the presence of sufficient testosterone levels (24).…”

Characterization of β-defensin 42 expressed in principal cells at the initial segment of the rat epididymis

“…It was reported that significant reductions occurred in lumen diameter and epithelial height following efferent duct ligation (EDL), and such changes were likely the consequences of altered gene expression [32]. The initial segment, the maintenance of its epithelia in particular, was regulated by luminal testicular fluids other than androgen [33]. Numerous genes in the initial segment, including 5α-reductase [34], CRES [35], mEP17 [36], A-raf [37], and Lcn9 [38], were regulated by luminal testicular fluids other than androgen.…”