Differential Regulation of Gonadotropin Receptors (fshr and lhcgr) by Estradiol in the Zebrafish Ovary Involves Nuclear Estrogen Receptors That Are Likely Located on the Plasma Membrane

FSH and LH are gonadotropins (GTH) that control all major events of gonadal function. FSH and LH signal through their cognate receptors, FSH receptor and LH/choriogonadotropin receptor, respectively, across vertebrates. Compared with the information in mammals, very little is known about these receptors in fish, especially the regulation of their expression. In female zebrafish, fshr and lhcgr exhibit significant temporal difference in expression, with fshr increasing first when the follicles are activated to enter the vitellogenic growth phase and lhcgr lagging behind. This raises an interesting question on the differential regulation of these two GTH receptors (GTHR) during folliculogenesis. Using a primary follicle cell culture, the present study demonstrated that 17 beta-estradiol (E2), but not testosterone, was a potent endocrine hormone that differentially regulated the expression of fshr and lhcgr. Although E2 stimulated both receptors, its effect on the steady-state level of lhcgr mRNA was much higher (>8-fold up-regulation) than that of fshr (similar to 0.5-fold increase). E2 likely acted at the transcription level via its nuclear estrogen receptors (ER alpha and ER beta), because ICI 182,780 could abolish its effects. However, our evidence suggested that these receptors might be localized on the plasma membrane, because beta-estradiol 6-(O-carboxy methyl) oxime:BSA could fully mimic the effects of E2. Demonstrating that E2 is likely one of the differentiating factors for the distinct expression of the two GTHR in the zebrafish ovary, this study sheds important light on the functions of the two GTH and their receptors in fish as well as the conservation and diverse aspects of GTHR regulation across vertebrates. (Endocrinology 152: 4418-4430, 2011)