Peripubertal ontogeny and estrogen stimulation of cholecystokinin and preproenkephalin mRNA in the rat hypothalamus and limbic system

Abstract

The neuropeptide cholecystokinin (CCK) is expressed in limbic system and hypothalamic nuclei that form a circuit that regulates the display of the female rodent reproductive behavior, lordosis. CCK mRNA and peptide levels fluctuate across the estrous cycle and have been shown to be modulated by estrogen exposure. The objective of these experiments was to examine the expression of CCK mRNA during postnatal development of this limbic-hypothalamic, lordosis regulating circuit, and to determine the age at which CCK mRNA expression becomes responsive to estrogen stimulation, by using quantitative in situ hybridization histochemistry. CCK mRNA levels were below the level of detectability within the circuit during the postnatal period, but increased during the peripubertal period. Rats were injected with either estradiol benzoate (EB), EB and progesterone, progesterone, or oil, and were killed 48 hours later on postnatal day (PND) 15, 20, and 25. Alternate brain sections were processed for CCK and preproenkephalin (PPE) mRNA in situ hybridization histochemistry. EB treatment induced CCK mRNA expression in the central portion of the medial preoptic nucleus and posterodorsal medial amygdala at PND 20 and 25, respectively. However, EB treatment increased PPE mRNA levels within the nuclei of the circuit at all ages examined. Progesterone had neither an independent nor additive effect on the EB induction of these neuropeptide messages. The estrogenic induction of CCK mRNA appears to be dependent on estrogen sensitive pathways of neurotransmission, or components of second messenger pathways which regulate CCK mRNA expression in the adult limbic-hypothalamic lordosis regulating circuit, which are not functional before PND 18-25.

Estrogen-Induced μ-Opioid Receptor Internalization in the Medial Preoptic Nucleus Is Mediated via Neuropeptide Y-Y1Receptor Activation in the Arcuate Nucleus of Female Rats

“…␦-Opioid receptors preferentially bind enkephalin, but ␤-END and the endomorphins preferentially bind to MOR and inhibit EB or EB plus progesterone-induced lordosis (Sirinathsinghji, 1984;Sinchak and Micevych, 2001). Enkephalin and ␤-END expression have been shown to be regulated by estrogen (Wilcox and Roberts, 1985;Priest et al, 1995;Holland et al, 1998). Although endomorphins are the most MOR-selective endogenous opioid peptides (Zadina et al, 1999), to date, no studies indicate a steroid or NPY regulation of endormorphin cells.…”

Dynamics of appetite-mediated gene expression in daidzein-fed female rats in the meal-feeding method

“…20,21) Estradiol treatment also induced CCK mRNA expression in the central portion of the medial preoptic nucleus and posterodorsal medial amygdale. 22) In the periphery, estradiol treatment elevated plasma levels of estradiol and CCK in a dose-dependent manner.…”

Estrogen receptor‐α is required for estrogen‐induced μ‐opioid receptor internalization

“…Estrogen induced internalization (activation) of the MOR+ in rats was reduced by blocking the intracellular receptor actions of estrogen with the ERα and ERβ selective ER modulator, tamoxifen (unpublished observations). ERs have been localized in cells expressing enkephalin and β‐endorphin (Morrell et al, 1985; Akesson and Micevych, 1991), and the expression of these peptides is highly regulated by estrogen (Romano et al, 1988; Priest et al, 1995; Holland et al, 1998; Priest and Roberts, 2000; reviewed in Hammer and Cheung, 1995). The expression of MOR‐active opioid peptides suggests that endogenous ligands are present in ERαKO mice.…”