title: Estrogens, but not androgens, regulate expression and functional activity of oxytocin receptor in rabbit epididymis.
abstract: Previous binding and contractility studies indicate that oxytocin (OT) receptors are present in rabbit epididymis. To investigate the effect of changing endocrine milieu on OT responsiveness, we induced hypogonadism (hypo) in rabbits with a single administration of a long-acting GnRH analog, triptorelin, and we replaced hypogonadal rabbits with different sex steroids. After 2 months from triptorelin administration, testosterone (T) plasma levels were decreased and OT responsiveness abolished. Administration of T to hypo rabbits restored T plasma levels but not OT sensitivity. Because Western blot analysis indicated that both estrogen receptors and aromatase are expressed in the epididymis, we treated hypo rabbits with estradiol valerate (E2v). E2v not only completely restored OT responsiveness but also even amplified it. Accordingly, Northern and Western blot analysis indicated that both OT receptor gene and protein were strongly induced by E2v but not by T. Surprisingly, also the class I estrogen receptor antagonist, tamoxifen restored OT sensitivity in hypo rabbits. To verify whether endogenous estradiol is involved in the regulation of OT receptor responsiveness, we treated intact rabbits with an aromatase inhibitor, letrozole. Blocking aromatase activity almost completely abolished OT sensitivity. These findings suggest a new function of estrogens in the male: regulation of OT responsiveness in epididymis.
authors.affiliation: Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence 50139, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Filippi
authors.forename: Michaela
authors.initials: M
authors.lastname: Luconi
authors.forename: Simone
authors.initials: S
authors.lastname: Granchi
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
authors.forename: Saverio
authors.initials: S
authors.lastname: Bettuzzi
authors.forename: Paola
authors.initials: P
authors.lastname: Tozzi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ledda
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000728:Androgens / Q000502:physiology*; D000818:Animals; D047072:Aromatase Inhibitors; D015152:Blotting, Northern; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004822:Epididymis / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005786:Gene Expression Regulation; D007006:Hypogonadism / Q000139:chemically induced / Q000378:metabolism; D000077289:Letrozole; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000097:blood / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D017329:Triptorelin Pamoate / Q000008:administration & dosage
chemical_list: D000728:Androgens; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004967:Estrogens; D009570:Nitriles; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D014230:Triazoles; D017329:Triptorelin Pamoate; D013629:Tamoxifen; D013739:Testosterone; D004958:Estradiol; D010121:Oxytocin; D000077289:Letrozole