title: Nuclear receptor coactivators function in estrogen receptor- and progestin receptor-dependent aspects of sexual behavior in female rats.
abstract: The ovarian hormones, estradiol (E) and progesterone (P) facilitate the expression of sexual behavior in female rats. E and P mediate many of these behavioral effects by binding to their respective intracellular receptors in specific brain regions. Nuclear receptor coactivators, including Steroid Receptor Coactivator-1 (SRC-1) and CREB Binding Protein (CBP), dramatically enhance ligand-dependent steroid receptor transcriptional activity in vitro. Previously, our lab has shown that SRC-1 and CBP modulate estrogen receptor (ER)-mediated induction of progestin receptor (PR) gene expression in the ventromedial nucleus of the hypothalamus (VMN) and hormone-dependent sexual receptivity in female rats. Female sexual behaviors can be activated by high doses of E alone in ovariectomized rats, and thus are believed to be ER-dependent. However, the full repertoire of female sexual behavior, in particular, proceptive behaviors such as hopping, darting and ear wiggling, are considered to be PR-dependent. In the present experiments, the function of SRC-1 and CBP in distinct ER- (Exp. 1) and PR- (Exp. 2) dependent aspects of female sexual behavior was investigated. In Exp. 1, infusion of antisense oligodeoxynucleotides to SRC-1 and CBP mRNA into the VMN decreased lordosis intensity in rats treated with E alone, suggesting that these coactivators modulate ER-mediated female sexual behavior. In Exp. 2, antisense to SRC-1 and CBP mRNA around the time of P administration reduced PR-dependent ear wiggling and hopping and darting. Taken together, these data suggest that SRC-1 and CBP modulate ER and PR action in brain and influence distinct aspects of hormone-dependent sexual behaviors. These findings support our previous studies and provide further evidence that SRC-1 and CBP function together to regulate ovarian hormone action in behaviorally-relevant brain regions.
authors.affiliation: Center for Neuroendocrine Studies, Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA 01003, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Molenda-Figueira
authors.forename: Casey A
authors.initials: CA
authors.lastname: Williams
authors.forename: Andreana L
authors.initials: AL
authors.lastname: Griffin
authors.forename: Eric M
authors.initials: EM
authors.lastname: Rutledge
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Blaustein
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Tetel
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000032:analysis / Q000502:physiology*; D005260:Female; D051548:Histone Acetyltransferases / Q000235:genetics / Q000502:physiology*; D008297:Male; D008845:Microinjections; D056920:Nuclear Receptor Coactivator 1; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D011187:Posture; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; D050882:CREB-Binding Protein; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1