Developmental expression profiles and distinct regional estrogen responsiveness suggest a novel role for the steroid receptor coactivator SRC-1 as discriminative amplifier of estrogen signaling in the rat brain.
The regional distribution, developmental profiles, and gonadectomy- and estrogen-induced changes in the density of transcripts encoding the steroid receptor coactivator-1 (SRC-1) were examined in the female rat brain by semiquantitative in situ hybridization. The results demonstrate striking differences in the abundance of SRC-1 mRNA in discrete brain regions throughout ontogeny. Whereas transcript densities gradually decreased with age in the cerebral cortex, they peaked prominently during the peripubertal period in the hypothalamic medial preoptic area (MPOA) and ventromedial nucleus (VMN). Gonadectomy and estrogen substitution influenced SRC-1 mRNA levels in sexually mature animals in a region-specific fashion. Ovariectomy resulted in a down-regulation of SRC-1 mRNA levels in the VMN, a brain region richly endowed with estrogen receptors and playing a major role in neuroendocrine control of reproductive functions. In contrast, SRC-1 transcript levels were significantly up-regulated after estradiol treatment. Interestingly, SRC-1 expression in the cortex was refractory to alterations of the estrogen milieu. The obtained SRC-1 mRNA expression profiles during development clearly demonstrate brain region specificity and regulation by estrogen, thus it is proposed that SRC-1 amplifies estrogen receptor-dependent transcription in a temporally and spatially coordinated manner and therefore contributes to the functional specialization of brain areas involved in the regulation of reproduction.
Mitev
Yuri A
YA
Gender Health Care Research, Schering AG/Jenapharm, 07745 Jena, Germany.
Wolf
Siegmund S
SS
Almeida
Osborne F X
OF
Patchev
Vladimir K
VK
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases; D008954:Models, Biological; D056920:Nuclear Receptor Coactivator 1; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D004967:Estrogens; D012333:RNA, Messenger; D014157:Transcription Factors; D004958:Estradiol; D051548:Histone Acetyltransferases; D056920:Nuclear Receptor Coactivator 1