title: The catecholestrogen, 2-hydroxyestradiol-17beta, acts as a G protein-coupled estrogen receptor 1 (GPER/GPR30) antagonist to promote the resumption of meiosis in zebrafish oocytes.
abstract: Estradiol-17beta (E2) maintains high cAMP levels and meiotic arrest in zebrafish oocytes through activation of G protein-coupled estrogen receptor (GPER). The catecholestrogen 2-hydroxyestradiol-17beta (2-OHE2) has an opposite effect to that of E2 on oocyte maturation (OM) and cAMP levels in Indian catfish oocytes. We tested the hypothesis that 2-OHE2 is produced in zebrafish ovaries and promotes the resumption of oocyte meiosis through its action as a GPER antagonist. Ovarian 2-OHE2 production by estrogen-2-hydroxylase (EH) was up-regulated by gonadotropin treatment at the onset of OM, consistent with a physiological role for 2-OHE2 in regulating OM. The increases in EH activity and OM were blocked by treatment with CYP1A1 and CYP1B1 inhibitors. Expression of cyp1a, cyp1b1, and cyp1c mRNAs was increased by gonadotropin treatment, further implicating these Cyp1s in 2-OHE2 synthesis prior to OM. Conversely, aromatase activity and cyp19a1 mRNA expression declined during gonadotropin induction of OM. 2-OHE2 treatment significantly increased spontaneous OM in defolliculated zebrafish oocytes and reversed the inhibition of OM by E2 and the GPER agonist G-1. 2-OHE2 was an effective competitor of [(3)H]-E2 binding to recombinant zebrafish GPER expressed in HEK-293 cells. 2-OHE2 also antagonized estrogen actions through GPER on cAMP production in zebrafish oocytes, resulting in a reduction in cAMP levels. Stimulation of OM by 2-OHE2 was blocked by pretreatment of defolliculated oocytes with the GPER antibody. Collectively, the results suggest that 2-OHE2 functions as a GPER antagonist and promotes OM in zebrafish through blocking GPER-dependent E2 inhibition of the resumption of OM.
authors.affiliation: University of Texas at Austin, Marine Science Institute, Port Aransas, Texas.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Chourasia
authors.affiliation: University of Texas at Austin, Marine Science Institute, Port Aransas, Texas.
authors.forename: Yefei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: University of Texas at Austin, Marine Science Institute, Port Aransas, Texas peter.thomas@utexas.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D008540:Meiosis / Q000187:drug effects* / Q000502:physiology; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism; D009866:Oogenesis / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013250:Steroid Hydroxylases / Q000378:metabolism; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors*
chemical_list: D002393:Estrogens, Catechol; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C549840:gper1 protein, zebrafish; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; C001390:2-hydroxyestradiol; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase
keywords: 2-OHE2; 2-hydroxyestradiol-17β; GPER; GPER antagonist; GPR30; catecholestrogen; oocyte maturation; zebrafish