title: Characterization of Ovarian Responses to Equine Chorionic Gonadotropin of Aromatase-Deficient Mice With or Without 17β-Estradiol Supplementation.
abstract: Aromatase is an enzyme catalyzing the final step of 17β-estradiol (E2) biosynthesis. Aromatase-deficient (ArKO) mice displayed vital roles of E2 at various tissue sites, including ovary. Here, we report attenuated responses of ArKO ovary to equine chorionic gonadotropin (eCG), an alternative to FSH. Ovarian contents of cAMP and anti-Müllerian hormone (AMH), putative factors reducing sensitivity to gonadotropins, were significantly elevated in ArKO mice compared with those in wild type (WT) mice in the basal state. Accordingly, eCG-induced ovarian alterations in cAMP contents, phosphorylation levels of signaling molecules, and mRNA expression of eCG-targeted genes were blunted in ArKO mice compared with those in WT mice. Treatment of ArKO mice with E2 decreased ovarian cAMP and AMH contents to the WT levels but did not restore the sensitivity. Microarray analysis coupled with quantitative RT-PCR analysis identified 7 genes of which the mRNA expression levels in ArKO ovaries were significantly different from those in the WT ovaries in the basal state and were not normalized by E2 supplementation, indicating possible involvement of these gene products in the determination of ovarian sensitivity to eCG. Thus, present analyses revealed that estrogen deficiency attenuates sensitivity of the ovary to gonadotropin, which might be associated with alterations in the ovarian contents of multiple molecules including cAMP and AMH. Given the importance of the ovarian responses to gonadotropins in reproductive function, detailed knowledge about the underlying mechanisms of abnormalities in the ArKO ovary might help to develop potential targets for infertility treatments.
authors.affiliation: Departments of Biochemistry (K.T.), Pathology (Y.H.), and Gastroenterology and Hepatology (M.O., T.S.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Toda
authors.affiliation: Departments of Biochemistry (K.T.), Pathology (Y.H.), and Gastroenterology and Hepatology (M.O., T.S.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Departments of Biochemistry (K.T.), Pathology (Y.H.), and Gastroenterology and Hepatology (M.O., T.S.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.affiliation: Departments of Biochemistry (K.T.), Pathology (Y.H.), and Gastroenterology and Hepatology (M.O., T.S.), Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D000242:Cyclic AMP; D001141:Aromatase