PMID- 23415714 OWN - NLM STAT- MEDLINE DCOM- 20130916 LR - 20141120 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 369 IP - 1-2 DP - 2013 Apr 30 TI - Androgen/androgen receptor pathway regulates expression of the genes for cyclooxygenase-2 and amphiregulin in periovulatory granulosa cells. PG - 42-51 LID - S0303-7207(13)00062-2 [pii] LID - 10.1016/j.mce.2013.02.004 [doi] AB - It is well known that the androgen/androgen receptor (AR) pathway is involved in both male and female fertility in mammals. AR knockout female mice are reported to exhibit various abnormalities in follicle development, and a subfertile phenotype. In exogenous gonadotropin-induced superovulation, serum androgen levels were robustly elevated in female mice at the periovulatory stage after human chorionic gonadotropin (hCG) treatment. At this stage, ovarian AR proteins were strongly expressed in cumulus cells. Because these results suggested that the androgen/AR pathway is involved in ovulation, we investigated the expression of ovulation-related genes in the mouse ovary treated with the nonaromatizable androgen, 5alpha-dihydrotestosterone (DHT). DHT treatment induced the expression of the genes for cyclooxyganase-2 (Cox-2 or prostaglandin endoperoxidase synthase 2) and the epidermal growth factor-like factor, amphiregulin (Areg), in the ovary, whereas their hCG-induced expression was suppressed by the AR antagonist flutamide. These genes were also induced by DHT in AR-expressing primary granulosa and granulosa tumor-derived cells. Reporter assays, electrophoretic shift mobility assays and chromatin immunoprecipitation assays demonstrated that androgen response sequence(s) existing upstream of each gene were responsible for androgen responsiveness and were occupied by the AR in periovulatory granulosa cells. Our results suggest that the androgen/AR pathway is involved in the ovulatory process via expression of the Cox-2 and Areg genes in periovulatory granulosa cells. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Yazawa, Takashi AU - Yazawa T AD - Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Matsuoka, Fukui, Japan. yazawa@u-fukui.ac.jp FAU - Kawabe, Shinya AU - Kawabe S FAU - Kanno, Masafumi AU - Kanno M FAU - Mizutani, Tetsuya AU - Mizutani T FAU - Imamichi, Yoshitaka AU - Imamichi Y FAU - Ju, Yunfeng AU - Ju Y FAU - Matsumura, Takehiro AU - Matsumura T FAU - Yamazaki, Yukiko AU - Yamazaki Y FAU - Usami, Yoko AU - Usami Y FAU - Kuribayashi, Mayu AU - Kuribayashi M FAU - Shimada, Masayuki AU - Shimada M FAU - Kitano, Takeshi AU - Kitano T FAU - Umezawa, Akihiro AU - Umezawa A FAU - Miyamoto, Kaoru AU - Miyamoto K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130213 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Androgen Receptor Antagonists) RN - 0 (Androgens) RN - 0 (Areg protein, mouse) RN - 0 (Chorionic Gonadotropin) RN - 0 (EGF Family of Proteins) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 08J2K08A3Y (Dihydrotestosterone) RN - 76W6J0943E (Flutamide) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Amphiregulin MH - Androgen Receptor Antagonists/pharmacology MH - Androgens/*pharmacology MH - Animals MH - Chorionic Gonadotropin/pharmacology MH - Cyclooxygenase 2/genetics/*metabolism MH - Dihydrotestosterone/*pharmacology MH - EGF Family of Proteins MH - Female MH - Flutamide/pharmacology MH - Glycoproteins/genetics/*metabolism MH - Granulosa Cells/drug effects/*metabolism MH - Intercellular Signaling Peptides and Proteins/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL EDAT- 2013/02/19 06:00 MHDA- 2013/09/17 06:00 CRDT- 2013/02/19 06:00 PHST- 2012/09/04 00:00 [received] PHST- 2012/12/26 00:00 [revised] PHST- 2013/02/05 00:00 [accepted] PHST- 2013/02/19 06:00 [entrez] PHST- 2013/02/19 06:00 [pubmed] PHST- 2013/09/17 06:00 [medline] AID - S0303-7207(13)00062-2 [pii] AID - 10.1016/j.mce.2013.02.004 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2013 Apr 30;369(1-2):42-51. doi: 10.1016/j.mce.2013.02.004. Epub 2013 Feb 13.