title: Gonadotropin-releasing hormone and gonadal steroids regulate transcription factor mRNA expression in primary pituitary and immortalized gonadotrope cells.
abstract: Hormonal regulation of pituitary gonadotropin gene expression has been attributed to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early gene expression and gonadal steroid interactions with their respective nuclear receptors. A number of orphan nuclear receptors including steroidogenic factor 1, liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter-transcription factors I/II as well as the GATA family members, GATA2 and GATA4, have also been implicated in transcriptional regulation of the gonadotropin genes. We hypothesized that hormonally mediated changes in these latter transcription factors may provide an additional mechanism for mediating hormonal effects beyond the more classically appreciated pathways. In these studies, we demonstrate significant regulation of orphan nuclear receptor and GATA messenger RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both cultured primary pituitary cells and gonadotrope-derived cell line, LβT2. These results advance our understanding of the complex mechanisms by which GnRH and steroid hormones achieve precise regulation of anterior pituitary function.
authors.affiliation: Core Laboratories, St. Paul University Hospital, Dallas, TX, USA.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Green Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Constance M
authors.initials: CM
authors.lastname: Grafer
authors.affiliation: Houston Fertility Institute, Houston, TX, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Rockville, MD, USA lhalvo@gmail.com.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Halvorson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006066:Gonads / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D050989:GATA2 Transcription Factor; D050991:GATA4 Transcription Factor; C494713:Gata2 protein, rat; C084365:Gata4 protein, rat; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D014157:Transcription Factors; D013196:Dihydrotestosterone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol
keywords: GnRH; gonadal steroids; pituitary; transcription factor