Differential expression and regional distribution of steroid receptor coactivators SRC-1 and SRC-2 in brain and pituitary

Members of the p160 family of steroid receptor coactivator proteins mediate the stimulatory effects on gene transcription brought about by nuclear rec eptors, which comprise all steroid receptors. Using in situ hybridization w e have examined the neuroanatomical distribution of the messenger RNAs (mRN As) for two functionally distinct splice variants of Steroid Receptor Coact ivator 1 (SRC-1/NCoA-1) and of Steroid Receptor Coactivator 2 (SRC-2INCoA-2 /GRIP-1/TIF-2). Transcripts encoding these coactivators show highly differe ntial expression patterns. SRC-3 mRNA is expressed at very low levels in br ain, but shows expression in the anterior pituitary. SRC-la and le mRNA are expressed in many brain areas, including hippocampus, amygdala, hypothalam us, basal ganglia, and isocortex. Striking differences between SRC-la and l e expression were observed in several brain nuclei. Relative levels of SBC- 1a mRNA were much higher in anterior pituitary, and the arcuate, paraventri cular and ventromedial nucleus of the hypothalamus, the locus coeruleus and the trigeminal motor nucleus, all important targets of steroid hormones in the brain. SRC-le mRNA showed modest elevation of relative expression in t he caudal nucleus accumbens (shell), basolateral amygdala, and some thalami c nuclei. The differential and uneven neuroanatomical distribution of these coactivators may underlie diversity and cell-specificity of steroid recept or mediated signals in the brain.