Cells in behaviourally relevant brain regions coexpress nuclear receptor coactivators and ovarian steroid receptors

Oestradiol and progesterone act in the brain to elicit profound effects on behaviour and physiology. One physiological function of oestradiol is the induction of progesterone receptor (PR) expression in a variety of behaviourally relevant brain regions, including the ventromedial nucleus of the hypothalamus (VMN), the medial preoptic nucleus of the preoptic area (MPOA), the arcuate nucleus (ARC) and the medial central grey (MCG). Ligand-dependent transcriptional activity of steroid receptors, including oestrogen receptors (ER) and Pr, is dramatically influenced by nuclear receptor coactivators. In previous studies, we have found that two of these nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP), are important in ER-mediated induction of PR in the VMN and in steroid-dependent behaviours. For nuclear receptor coactivators to function in hormone-dependent transcription in the brain and regulate behaviour, both receptor and coactivator must be expressed in the same cell. In the present study, we used a dual-label immunohistochemical technique to investigate if individual cells in behaviourally relevant brain regions coexpress nuclear receptor coactivators and steroid receptors. Confocal analysis revealed that in oestrogen-primed rats, most of the E-induced PR cells in the VMN (89.6%), MPOA (63%), ARC (82.6%), and many in the MCG (39%), also express SRC-1. In addition, the majority of the cells containing E-induced PR in the VMN (78.3%), MPOA (83.1%), ARC (83.6%), and MCG (60%) also express CBP. These results, taken together with the findings that virtually all oestradiol-induced PR containing cells in the brain express ER, suggest that these neurones represent sites of functional interaction of nuclear receptor coactivators with ovarian steroid receptors in the brain. The present findings provide neuroanatomical evidence that nuclear receptor coactivators are integral in mediating steroid hormone action in behaviourally relevant brain regions.