Identification of estradiol/ERα-regulated genes in the mouse pituitary

J Endocrinol. 2011 Sep;210(3):309-21. doi: 10.1530/JOE-11-0098. Epub 2011 Jun 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Estradiol / metabolism*
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / deficiency
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Estrus / genetics
  • Estrus / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Gonadotropin-Releasing Hormone / metabolism
  • Gonadotropin-Releasing Hormone / pharmacology
  • In Vitro Techniques
  • Luteinizing Hormone / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • DNA Primers
  • Estrogen Receptor alpha
  • RNA, Messenger
  • Gonadotropin-Releasing Hormone
  • Estradiol
  • Luteinizing Hormone