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 E2 (17β-estradiol) replacement, acyline (GnRH antagonist) and flutamide (anti-androgen) treatment on the ovarian phenotype of ArKO mice. E2 replacement and acyline treatment but not flutamide treatment, reduced serum gonadotrophin levels of ArKO mice to within normal ranges. E2 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.