title: ESR1 inhibits hCG-induced steroidogenesis and proliferation of progenitor Leydig cells in mice.
abstract: Oestrogen is an important regulator in reproduction. To understand the role of oestrogen receptor 1 (ESR1) in Leydig cells, we investigated the expression of ESR1 in mouse Leydig cells during postnatal development and the effects of oestrogen on steroidogenesis and proliferation of progenitor Leydig cells (PLCs). In Leydig cells, the ESR1 expression was low at birth, increased until postnatal day 14 at which PLCs were predominant, and then decreased until adulthood. In foetal Leydig cells, ESR1 immunoreactivity increased from birth to postnatal day 14. These suggest that ESR1 is a potential biomarker of Leydig cell development. In PLCs, 17β-estradiol and the ESR1-selective agonist propylpyrazoletriol suppressed human chorionic gonadotropin (hCG)-induced progesterone production and steroidogenic gene expression. The ESR2-selective agonist diarylpropionitrile did not affect steroidogenesis. In PLCs from Esr1 knockout mice, hCG-stimulated steroidogenesis was not suppressed by 17β-estradiol, suggesting that oestrogen inhibits PLC steroidogenesis via ESR1. 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile decreased bromodeoxyuridine uptake in PLCs in the neonatal mice. In cultured PLCs, 17β-estradiol, propylpyrazoletriol, and diarylpropionitrile reduced hCG-stimulated Ki67 and Pcna mRNA expression and the number of KI67-positive PLCs, suggesting that oestrogen inhibits PLC proliferation via both ESR1 and ESR2. In PLCs, ESR1 mediates the oestrogen-induced negative regulation of steroidogenesis and proliferation.
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
authors.forename: Yeong Seok
authors.initials: YS
authors.lastname: Oh
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
authors.forename: Il Kyoo
authors.initials: IK
authors.lastname: Koh
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Life Science and Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Korea.
authors.forename: Myung Chan
authors.initials: MC
authors.lastname: Gye
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D061251:Primary Cell Culture; D011374:Progesterone / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D006063:Chorionic Gonadotropin; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; D009570:Nitriles; D010636:Phenols; D018809:Proliferating Cell Nuclear Antigen; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D001973:Bromodeoxyuridine