First Author | Alves SE | Year | 2000 |
Journal | J Comp Neurol | Volume | 427 |
Issue | 2 | Pages | 185-95 |
PubMed ID | 11054687 | Mgi Jnum | J:65530 |
Mgi Id | MGI:1926703 | Doi | 10.1002/1096-9861(20001113)427:2<185::aid-cne2>3.0.co;2-g |
Citation | Alves SE, et al. (2000) Estrogen-regulated progestin receptors are found in the midbrain raphe but not hippocampus of estrogen receptor alpha (ERalpha) gene-disrupted mice. J Comp Neurol 427(2):185-95 |
abstractText | Estrogen and progesterone may modulate serotonergic function through intracellular receptors, alpha (ERalpha) and/or beta (ERbeta), and the progestin receptor (PR). Studies in macaque and rat suggest species differences in steroid action. Presently, we examined the mouse. To identify whether ERalpha is involved in estrogen induction of PR in midbrain raphe, we studied the ERalpha gene-disrupted (alphaERKO) mouse. The hippocampus was examined as another estrogen/progestin-sensitive brain area reported to express ERalpha, ERbeta, and PR. Female and male homozygous alphaERKO and wildtype mice were gonadectomized and given estradiol benzoate or vehicle. Dual-label immunocytochemistry was performed for PR or ERalpha and the serotonin-synthesizing enzyme, tryptophan hydroxylase (TPH). Cells exhibiting PR immunoreactivity (PR-ir) or ERalpha-ir were observed in dorsal and median raphe and hippocampus in both sexes. No ERalpha-ir cells were observed in alphaERKO brains. In raphe, PR-ir or ERalpha-ir often colocalized with TPH-ir. Thus, estrogen and progesterone may directly modulate gene expression in select serotonergic neurons via ERalpha and PR in female and male mice. Estrogen significantly increased the number of PR-ir cells, and the percentage of PR-ir cells colocalizing TPH-ir in both raphe nuclei, regardless of sex and genotype. Although less among alphaERKO mice, the significant estrogen induction of PRs implicates the involvement of another ER, perhaps ERbeta. In hippocampus, distinct estrogen-induced PR-ir cells were observed only in wildtype animals, demonstrating an ERalpha-mediated event in this forebrain region. Collectively, these findings suggest that estrogen can regulate the expression of one gene (the PR) via multiple mechanisms, based upon brain region. Copyright 2000 Wiley-Liss, Inc. |