Regulation of Progestin Receptors in Raphe Neurons of Steroid-Treated Monkeys

Abstract

Progesterone increases prolactin secretion in estrogen-primed primates. This action is probably mediated through a neural mechanism since lactotropes do not have progestin receptors (PR). This laboratory recently reported localization of PR in serotonin neurons of female macaques. Since serotonin (5HT) is a putative prolactin stimulatory agent, it was of interest to examine the regulation of PR in this neural system. Spayed monkeys were treated with either (1) an empty silastic capsule; (2) an estrogen (E)-filled capsule for 28 days, or (3) an E-filled capsule for 28 days supplemented with a progesterone (P)-filled capsule for the last 14 of the 28 days. Pontine tissue blocks were obtained at autopsy and processed for immunocytochemistry. Adjacent sections (10 µm) throughout the extent of the raphe nuclei were immunostained for 5HT and PR. 5HT-positive and PR-positive cells were counted in the same area of the dorsal and ventral raphe of adjacent sections at 4 representative levels and the PR/5HT ratio was calculated. The number of 5HT-positive cells was not different in spayed, E- or E+P-treated groups. E-treatment significantly increased the number of PR-positive cells and the PR/5HT ratio in the dorsal and ventral raphe. Supplementary P treatment did not significantly decrease the PR/5HT ratio in these areas. This data suggests that E induces PR in the 5HT neuronal system and that the expression of PR is maintained in the presence of chronically elevated progestin. Thus, the expression of PR in the raphe is consistent with the manner in which P increases prolactin secretion in estrogen-primed primates.

Estrogen and Progesterone Prevent Disruption of Prepulse Inhibition by the Serotonin-1A Receptor Agonist 8-Hydroxy-2-dipropylaminotetralin

“…Both estrogen and progesterone receptors are located in this nucleus in the rat (Alves et al, 1998). In addition, estrogen induces progesterone receptor expression in the dorsal raphe nucleus (Bethea, 1994). Previous studies have suggested that estrogen reduces 5-HT 1A receptor gene expression and the addition of progesterone enhances this effect on 5-HT 1A autoreceptors (Pecins- Thompson and Bethea, 1999) but reverses the effect of estrogen on the postsynaptic 5-HT 1A receptors (Birzniece et al, 2001).…”

Serotonin in microdialysate from the mediobasal hypothalamus increases after progesterone administration to estrogen primed macaques

“…We showed that serotonin neurons in monkeys express the nuclear form of the progestin receptor (Bethea, 1993;1994) and this receptor is markedly induced in animals treated with estrogen for several weeks. We previously showed that the mixed progestin receptor antagonist RU486 blocked P-induced prolactin secretion (Pecins-Thompson and Bethea, 1997).…”

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

“…This laboratory has shown that HT increases tryptophan hydroxylase production in the dorsal raphe nucleus Sanchez et al, 2005) and serotonin release in the hypothalamus (Centeno et al, 2007). Serotonin neurons express ERb and PR for mediation of the action of ovarian hormones (Bethea, 1993(Bethea, , 1994Gundlah et al, 2000Gundlah et al, , 2001. Thus, serotonin innervation of the PVN could mediate the decrease in CRH expression, but either an inhibitory serotonin receptor is required or more likely, an inhibitory GABA interneuron is present.…”