title: 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.
authors.affiliation: Department of Neurobiology, Brain Research Institute, Los Angeles, California 90095-1763, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Holland
authors.forename: L A
authors.initials: LA
authors.lastname: Norby
authors.forename: P E
authors.initials: PE
authors.lastname: Micevych
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000096:biosynthesis*; D004745:Enkephalins / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D017403:In Situ Hybridization; D008032:Limbic System / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis*; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004745:Enkephalins; D004967:Estrogens; D011498:Protein Precursors; D015347:RNA Probes; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D002766:Cholecystokinin; C033660:preproenkephalin