Estrogen sulfotransferase: discrete and androgen-dependent expression in the male reproductive tract and demonstration of an in vivo function in the mouse epididymis.
Estrogen sulfotransferase (EST) catalyzes the sulfoconjugation and inactivation of the steroid hormone estrogen. It is known previously that EST is expressed abundantly in Leydig cells of the testis. We recently have shown that male mice with targeted EST gene disruption developed age related Leydig cell and seminiferous tubule abnormalities as a consequence of increased local estrogen stimulation. In the same study, we also found that epididymal sperm isolated from the mutant mice had significantly reduced motility, but whether this reflected impaired epididymal function or was secondary to the testicular lesions was not known. The purpose of the current study was to investigate if EST is normally present in the mouse epididymis and/or other parts of the male reproductive tract where, as in testis, it may play a role in regulating local estrogen homeostasis. We describe here that EST is expressed in the epithelium of corpus and cauda but not caput regions of the mouse epididymis. It is also expressed in the luminal epithelium and smooth muscle cells of the vas deferens but was present at very low levels, if at all, in the prostate or seminal vesicle/ coagulating gland. Hypophysectomy, castration, and epididymal ligation experiments, together with the use of an androgen receptor antagonist, established that EST expression in the epididymis and vas deferens is critically dependent on pituitary hormone(s) and androgen but not on other factors in the testicular fluid. Administration of exogenous estradiol to mice with surgically ligated epididymis resulted in a more pronounced reduction in sperm motility in EST mutant mice than in wild-type mice. We conclude that EST is discretely expressed and regulated in the male reproductive tract and plays a physiological role in maintaining the functional integrity of the epididymis by regulating luminal estrogen homeostasis.
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
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D000728:Androgens / Q000502:physiology; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D013081:Sperm Motility; D015238:Sulfotransferases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014649:Vas Deferens / Q000201:enzymology
D000728:Androgens; D006063:Chorionic Gonadotropin; D004967:Estrogens; D012333:RNA, Messenger; D007986:Luteinizing Hormone; D015238:Sulfotransferases; C020122:estrone sulfotransferase