IMMUNOCYTOCHEMICAL LOCALIZATION OF NUCLEAR ESTROGEN-RECEPTORS AND PROGESTIN RECEPTORS WITHIN THE RAT DORSAL RAPHE NUCLEUS

Estradiol and progesterone modulate central serotonergic activity; how ever, the mechanism(s) of action remain unclear. Recently estradiol-in duced progestin receptors (PRs) have been localized within the majorit y of serotonin (5-HT) neurons in the female macaque dorsal raphe nucle us (DRN; Bethea [1994] Neuroendocrinology 60:50-61). In the present st udy, we investigated whether estrogen receptors (ERs) and/or PRs exist within 5-HT and/or non-5-HT cells in the female and male rat DRN and whether estradiol treatment alters the expression of these receptors. Young adult female and male Sprague-Dawley rats were gonadectomized, a nd 1 week later, half of the animals received a subcutaneous Silastic implant of estradiol-17 beta. Animals were transcardially perfused 2 d ays later with acrolein and paraformaldehyde, and sequential dual-labe l immunocytochemistry was performed on adjacent sections by using eith er a PR antibody or an ER alpha antibody. This was followed by an anti body to either the 5-HT-synthesizing enzyme, tryptophan hydroxylase (T PH), or to the astrocytic marker, glial fibrillary acidic protein (GFA P). Cells containing immunoreactivity (ir) for nuclear ERs or PRs were identified within the rat DRN in a region-specific distribution in bo th sexes. No colocalization of nuclear ER-ir or PR-ir with cytoplasmic TPH-ir or GFAP-ir was observed in either sex or treatment; indicating that the steroid target cells are neither 5-HT neurons nor astrocytes . Females were found to have approximately 30% more PR-labeled cells c ompared with males throughout the DRN (P < 0.05), but no sex differenc e was detected in the number of neurons demonstrating ER-ir. In both s exes, 2 days of estradiol exposure decreased the number of cells with ER-ir, whereas it greatly increased the number of cells containing PR- ir in several DRN regions (P < 0.005). Collectively, these findings de monstrate the existence of nonserotonergic cells that-contain nuclear ERs or PRs within the female and male rat DRN, including estradiol-ind ucible PRs. These findings point to a species difference in ovarian st eroid regulation of 5-HT activity between the macaque and the rat, per haps transsynaptically via local neurons in the rat brain. (C) 1998 Wi ley-Liss, Inc.