title: Nuclear receptor coactivators are coexpressed with steroid receptors and regulated by estradiol in mouse brain.
abstract: OBJECTIVE
  The steroid hormones, including estradiol (E) and progesterone, act in the brain to regulate female reproductive behavior and physiology. These hormones mediate many of their biological effects by binding to their respective intracellular receptors. The receptors for estrogens (ER) and progestins (PR) interact with nuclear receptor coactivators to initiate transcription of steroid-responsive genes. Work from our laboratory and others reveals that nuclear receptor coactivators, including steroid receptor coactivator-1 (SRC-1) and SRC-2, function in brain to modulate ER-mediated induction of the PR gene and hormone-dependent behaviors. In order for steroid receptors and coactivators to function together, both must be expressed in the same cells.
  
  
  METHODS
  Triple-label immunofluorescence was used to determine if E-induced PR cells also express SRC-1 or SRC-2 in reproductively relevant brain regions of the female mouse.
  
  
  RESULTS
  The majority of E-induced PR cells in the medial preoptic area (61%), ventromedial nucleus of the hypothalamus (63%) and arcuate nucleus (76%) coexpressed both SRC-1 and SRC-2. A smaller proportion of PR cells expressed either SRC-1 or SRC-2, while a few PR cells expressed neither coactivator. In addition, compared to control animals, 17β-estradiol benzoate (EB) treatment increased SRC-1 levels in the arcuate nucleus, but not the medial preoptic area or the ventromedial nucleus of the hypothalamus. EB did not alter SRC-2 expression in any of the three brain regions analyzed.
  
  
  CONCLUSIONS
  Taken together, the present findings identify a population of cells in which steroid receptors and nuclear receptor coactivators may interact to modulate steroid sensitivity in brain and regulate hormone-dependent behaviors in female mice. Given that cell culture studies reveal that SRC-1 and SRC-2 can mediate distinct steroid-signaling pathways, the present findings suggest that steroids can produce a variety of complex responses in these specialized brain cells.
authors.affiliation: Neuroscience Program, Wellesley College, Mass., USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Tognoni
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Chadwick
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Ackeifi
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Tetel
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D056920:Nuclear Receptor Coactivator 1 / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism
chemical_list: D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D056920:Nuclear Receptor Coactivator 1