[Show abstract][Hide abstract] ABSTRACT: Human epididymal protein 6 (HE6; also known as GPR64) is an orphan member of the LNB-7TM (B2) subfamily of G-protein-coupled receptors. Family members are characterized by the dual presence of a secretin-like (type
II) seven-transmembrane (7TM) domain and a long cell adhesion-like extracellular domain. HE6 is specifically expressed within
the efferent ductules and the initial segment of the epididymis, ductal systems involved in spermatozoon maturation. Here,
we report that targeted deletion of the 7TM domain of the murine HE6 gene results in male infertility. Mutant mice reveal
a dysregulation of fluid reabsorbtion within the efferent ductules, leading to a backup of fluid accumulation in the testis
and a subsequent stasis of spermatozoa within the efferent ducts. The fertility phenotype of HE6 knockout mice identifies
this receptor as a potential nonsteroidal, nontesticular target for future male contraceptives and identifies an in vivo function
for a member of this unusual gene family.
Full-text · Article · Nov 2004 · Molecular and Cellular Biology
[Show abstract][Hide abstract] ABSTRACT: Estrogens control a diversity of physiological functions in different tissues. In mammals, the organs of the female reproductive tract including the uterus, the vagina, the ovary (Jennings and Creasman 1997), the mammary gland (Lippman and Dickson 1987; Dickson and Lippman 1989; Prichard 1997; Satyaswaroop 1997), the pituitary, and the hypothalamus are major targets of estrogens. However, estrogens also influence nonreproductive organs and systems. In the liver, estrogens cause alterations in the production of plasmatic proteins and in lipid metabolism (Krattenmacher et al. 1994; Von Schoultz et al. 1989; Steingold et al. 1991). In addition, evidence has been accumulated within the last two decades demonstrating that estrogens exhibit an important regulatory impact on the bone (Turner 1997), the urogenital tract (Kelleher 1997), the cardiovascular system (Nathan and Chaudhuri 1997; Clarkson and Anthony 1997; Lobo 1990; Sarrel 1992; Foegh 1992), and on brain functions (McEwen et al. 1997; Halbreich 1997; Sherwin 1997 a,b; Henderson 1997; Birge 1997).