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Estrogen‐regulated progestin receptors are found in the midbrain raphe but not hippocampus of estrogen receptor alpha (ERα) gene‐disrupted mice
Author(s) -
Alves Stephen E.,
Mcewen Bruce S.,
Hayashi Shinji,
Korach Kenneth S.,
Pfaff Donald W.,
Ogawa Sonoko
Publication year - 2000
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/1096-9861(20001113)427:2<185::aid-cne2>3.0.co;2-g
Subject(s) - endocrinology , medicine , estrogen receptor alpha , estrogen receptor beta , estrogen , dorsal raphe nucleus , biology , estrogen receptor , serotonergic , tryptophan hydroxylase , alpha (finance) , receptor , serotonin , construct validity , patient satisfaction , nursing , cancer , breast cancer
Estrogen and progesterone may modulate serotonergic function through intracellular receptors, alpha (ERα) and/or beta (ERβ), and the progestin receptor (PR). Studies in macaque and rat suggest species differences in steroid action. Presently, we examined the mouse. To identify whether ERα is involved in estrogen induction of PR in midbrain raphe, we studied the ERα gene‐disrupted (αERKO) mouse. The hippocampus was examined as another estrogen/progestin‐sensitive brain area reported to express ERα, ERβ, and PR. Female and male homozygous αERKO and wildtype mice were gonadectomized and given estradiol benzoate or vehicle. Dual‐label immunocytochemistry was performed for PR or ERα and the serotonin‐synthesizing enzyme, tryptophan hydroxylase (TPH). Cells exhibiting PR immunoreactivity (PR‐ir) or ERα‐ir were observed in dorsal and median raphe and hippocampus in both sexes. No ERα‐ir cells were observed in αERKO brains. In raphe, PR‐ir or ERα‐ir often colocalized with TPH‐ir. Thus, estrogen and progesterone may directly modulate gene expression in select serotonergic neurons via ERα 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 αERKO mice, the significant estrogen induction of PRs implicates the involvement of another ER, perhaps ERβ. In hippocampus, distinct estrogen‐induced PR‐ir cells were observed only in wildtype animals, demonstrating an ERα‐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. J. Comp. Neurol. 427:185–195, 2000. © 2000 Wiley‐Liss, Inc.