title: Estrogenic induction of spermatogenesis in the hypogonadal (hpg) mouse: role of androgens.
abstract: Testicular development is arrested in the hypogonadal (hpg) mouse due to a congenital deficiency of hypothalamic gonadotropin-releasing hormone synthesis. Previous studies have demonstrated that chronic treatment of these mice with estradiol induces testicular maturation and qualitatively normal spermatogenesis, but it is not known whether these are direct effects via estrogen receptors expressed in the testis, or indirect actions via the pituitary gland. The aim of the current studies was to determine whether the actions of estradiol require the presence of androgens. Sensitive assays revealed that chronic estradiol treatment produced time-dependent increases in pituitary FSH production but no increases in pituitary LH or testicular testosterone content could be detected. As a functional test of androgen dependence, hpg mice were treated for 70 days with estradiol plus Casodex (bicalutamide), an androgen receptor antagonist. Casodex treatment markedly attenuated both the estradiol-induced increase in testicular weight and the proliferation of the seminiferous epithelium, as revealed by morphometric analysis. However, it did not affect the estradiol-induced increase in pituitary FSH content, nor did it affect estradiol-induced increases in the weight of the seminal vesicles and epididymides. We conclude that increased FSH production is not sufficient to explain the increase in testicular development induced by estradiol in hpg mice; there is a requirement for functional androgen receptors for induction of testicular growth.
authors.affiliation: School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Baines
authors.forename: Margaret O
authors.initials: MO
authors.lastname: Nwagwu
authors.forename: Edwina C
authors.initials: EC
authors.lastname: Furneaux
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kerr
authors.forename: Terry M
authors.initials: TM
authors.lastname: Mayhew
authors.forename: Francis J P
authors.initials: FJ
authors.lastname: Ebling
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D000077267:Fulvestrant; D007006:Hypogonadism / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009570:Nitriles; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014105:Tosyl Compounds; D014599:Uterus / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D000077267:Fulvestrant; D004958:Estradiol; D005640:Follicle Stimulating Hormone; C053541:bicalutamide