title: The hypogonadal (hpg) mouse as a model to investigate the estrogenic regulation of spermatogenesis.
abstract: The hypogonadal (hpg) mouse is an excellent animal model in which to investigate the mechanism of action of estrogens on spermatogenesis because it has arrested reproductive development without the need for surgical, endocrine, pharmacological or immunological intervention. Hpg mice are hypogonadotrophic and fail to show normal postnatal testicular development due to the congenital inability to synthesize gonadotropin-releasing hormone in the hypothalamus. The hpg testis remains responsive to gonadotropins and androgens in that fertility can be induced by treatment with these hormones. Surprisingly, chronic treatment with low concentrations of estradiol alone induces qualitatively normal spermatogenesis. The induction of testicular development by estradiol in hpg mice is accompanied by a paradoxical increase in FSH production. The actions of estradiol in hpg mice appear to be via genomic estrogen receptors, as concurrent treatment with estrogen-receptor antagonist ICI182,780 completely blocks these pituitary and testis responses. Concurrent treatment with the androgen receptor antagonist bicalutamide does not affect the estradiol-induced increase in pituitary FSH content, but markedly attenuates the estradiol-induced increase in testicular weight. Western blot analyses and immunohistochemistry provide evidence for estrogen-receptor alpha and beta expression in both pituitary gland and testis of the hpg mouse. Estradiol may therefore exert direct actions within the testes and/or indirect neuroendocrine actions via the release of FSH or other hormones from the pituitary gland, but its actions are dependent upon the availability of low levels of androgen within the testis.
authors.affiliation: School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. fran.ebling@nottingham.ac.uk
authors.forename: Francis J P
authors.initials: FJ
authors.lastname: Ebling
authors.forename: Margaret O
authors.initials: MO
authors.lastname: Nwagwu
authors.forename: Helen
authors.initials: H
authors.lastname: Baines
authors.forename: Michelle
authors.initials: M
authors.lastname: Myers
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kerr
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D023421:Models, Animal; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology; D012708:Sertoli Cells / Q000502:physiology; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology*; D013737:Testis / Q000187:drug effects / Q000254:growth & development
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol; D005640:Follicle Stimulating Hormone