The lack of estrogen and excess luteinizing hormone are responsible for the female ArKO mouse phenotype.
It remains to be established as to whether the absence of estrogen (direct) or the elevated levels of gonadotrophins and androgens (indirect) are responsible for the ArKO (aromatase knockout) ovarian phenotype. The aim of this study was to determine the effects of E(2) (17beta-estradiol) replacement, acyline (GnRH antagonist) and flutamide (anti-androgen) treatment on the ovarian phenotype of ArKO mice. E(2) replacement and acyline treatment but not flutamide treatment, reduced serum gonadotrophin levels of ArKO mice to within normal ranges. E(2) replacement improved uterine and ovarian follicular phenotypes and reduced the number of Sertoli-like filled cords by 62%. Acyline treatment reduced the number of hemorrhagic cysts and the number of Sertoli-like filled cords within ArKO ovaries. The data indicate that the absence of estrogen in concert with elevated levels of circulating gonadotrophins, principally LH, is responsible for the abnormal reproductive phenotype of the female ArKO mouse.
Liew
Seng H
SH
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia. Jason.liew@princehenrys.org
Drummond
Ann E
AE
Jones
Margaret E
ME
Findlay
Jock K
JK
D000818:Animals; D001141:Aromatase / Q000172:deficiency* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000172:deficiency* / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D010919:Placebos; D021381:Protein Transport / Q000187:drug effects; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013256:Steroids / Q000097:blood
D004967:Estrogens; D006062:Gonadotropins; D009842:Oligopeptides; D010919:Placebos; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D013256:Steroids; D004958:Estradiol; D005485:Flutamide; D007986:Luteinizing Hormone; D001141:Aromatase; C109238:acyline