Estrogen receptor alpha signaling pathways differentially regulate gonadotropin subunit gene expression and serum follicle-stimulating hormone in the female mouse.
Estrogen, acting via estrogen receptor (ER)alpha, regulates serum gonadotropin levels and pituitary gonadotropin subunit expression. However, the cellular pathways mediating this regulation are unknown. ERalpha signals through classical estrogen response element (ERE)-dependent genomic as well as nonclassical ERE-independent genomic and nongenomic pathways. Using targeted mutagenesis in mice to disrupt ERalpha DNA binding activity, we previously demonstrated that ERE-independent signaling is sufficient to suppress serum LH levels. In this study, we examined the relative roles of ERE-dependent and -independent estrogen signaling in estrogen regulation of LH, FSH, prolactin, and activin/inhibin subunit gene expression, pituitary LH and FSH protein content, and serum FSH levels. ERE-independent signaling was not sufficient for estrogen to induce pituitary prolactin mRNA or suppress pituitary LHbeta mRNA, LH content, or serum FSH in estrogen-treated ovariectomized mice. However, ERE-independent signaling was sufficient to reduce pituitary glycoprotein hormone alpha-subunit, FSHbeta, and activin-betaB mRNA expression. Together with previous serum LH results, these findings suggest ERE-independent ERalpha signaling suppresses serum LH via reduced secretion, not synthesis. Additionally, ERE-dependent and ERE-independent ERalpha pathways may distinctly regulate steps involved in the synthesis and secretion of FSH.
Glidewell-Kenney
C
C
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Weiss
J
J
Hurley
L A
LA
Levine
J E
JE
Jameson
J L
JL
D000818:Animals; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006062:Gonadotropins / Q000235:genetics*; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology
D047628:Estrogen Receptor alpha; D004967:Estrogens; D006062:Gonadotropins; D021122:Protein Subunits; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone