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and ERß Null Mice Indicate a Role for ERß in Follicular Maturation
Receptor Biology Section (J.M.A.E., J.F.C., M.M.Y., K.S.K.), Laboratory of Reproductive and Developmental Toxicology, Laboratory of Experimental Pathology (S.A.E.), and Biostatistics Branch (G.E.K.), National Institute of Environmental Health Sciences/National Institutes of Health, Research Triangle Park, North Carolina 27709
Address all correspondence and requests for reprints to: Dr. Kenneth S. Korach, Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences/National Institutes of Health, MD B3-02, P.O. Box 12233, Research Triangle Park, North Carolina 27709. E-mail: korach{at}niehs.nih.gov.
Both estrogen receptor (ER) 
and ß are expressed within the ovary and lack of either of these receptors affects ovarian function. In this study, the role of ER and ERß in folliculogenesis and ovulation was further analyzed. Evaluation of ovarian follicle populations in wild-type and ERß knockout (ßERKO) ovaries revealed reduced late antral growth and ovulatory capacity of ßERKO follicles, indicated by reduced numbers of large antral follicles and corpora lutea and increased atresia of large antral follicles. An in vitro culture system was used to study growth, rupture, and luteinization of wild-type, ER knockout (ERKO) and ßERKO ovarian follicles. ERKO follicles exhibited wild-type-like growth and ovulation rates but an increased capacity to synthesize estradiol. In contrast, ßERKO follicles showed a significant lack of progression from early antral to large antral stage, decreased estradiol production, and reduced ovulation. Expression patterns of several genes involved in follicle maturation and ovulation were analyzed in follicles grown in vitro. Ar, Pgr, and Has2 mRNA expression levels were the same among the three genotypes. However, ßERKO follicles showed reduced expression of Cyp19 mRNA during follicle maturation and reduced Lhcgr and Ptgs2 mRNA expression after human chorionic gonadotropin stimulus. Luteinization occurs normally in ERKO and ßERKO follicles, shown by increased progesterone secretion and increased cdkn1b mRNA expression after human chorionic gonadotropin. Collectively, these data indicate that ERß, but not ER, plays a direct role in folliculogenesis. ERß appears to facilitate follicle maturation from the early antral to the preovulatory stage.
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