title: Identification of estradiol/ERα-regulated genes in the mouse pituitary.
abstract: Estrogen acts to prime the pituitary prior to the GnRH-induced LH surge by undiscovered mechanisms. This study aimed to identify the key components that mediate estrogen action in priming the pituitary. RNA extracted from the pituitaries of metestrous (low estrogen) and proestrus (high estrogen) stage mice, as well as from ovariectomized wild-type and estrogen receptor α (ERα) knockout mice treated with 17β-estradiol (E(2)) or vehicle, was used for gene expression microarray. Microarray data were then aggregated, built into a functional electronic database, and used for further characterization of E(2)/ERα-regulated genes. These data were used to compile a list of genes representing diverse biological pathways that are regulated by E(2) via an ERα-mediated pathway in the pituitary. This approach substantiates ERα regulation of membrane potential regulators and intracellular vesicle transporters, among others, but not the basic components of secretory machinery. Subsequent characterization of six selected genes (Cacna1a, Cacna1g, Cited1, Abep1, Opn3, and Kcne2) confirmed not only ERα dependency for their pituitary expression but also the significance of their expression in regulating GnRH-induced LH secretion. In conclusion, findings from this study suggest that estrogen primes the pituitary via ERα by equipping pituitary cells with critical cellular components that potentiate LH release on subsequent GnRH stimulations.
authors.affiliation: Division of Reproductive Sciences, Department of Clinical Sciences, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Mary C
authors.initials: MC
authors.lastname: Gieske
authors.forename: Kourtney L
authors.initials: KL
authors.lastname: Trudgen
authors.forename: Susan
authors.initials: S
authors.lastname: Hudgins-Spivey
authors.forename: Beob Gyun
authors.initials: BG
authors.lastname: Kim
authors.forename: Andree
authors.initials: A
authors.lastname: Krust
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Eric
authors.initials: E
authors.lastname: Blalock
authors.forename: CheMyong
authors.initials: C
authors.lastname: Ko
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004971:Estrus / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone