Identification of estradiol/ERalpha-regulated genes in the mouse pituitary.

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Date publication

septembre 2011

Auteurs

Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre


Tous les auteurs :
Kim HJ, Gieske MC, Trudgen KL, Hudgins-Spivey S, Kim BG, Krust A, Chambon P, Jeong JW, Blalock E, Ko C

Résumé

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 alpha (ERalpha) knockout mice treated with 17beta-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)/ERalpha-regulated genes. These data were used to compile a list of genes representing diverse biological pathways that are regulated by E(2) via an ERalpha-mediated pathway in the pituitary. This approach substantiates ERalpha 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 ERalpha 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 ERalpha by equipping pituitary cells with critical cellular components that potentiate LH release on subsequent GnRH stimulations.

Référence

J Endocrinol. 2011 Sep;210(3):309-21