PERIPUBERTAL ONTOGENY AND ESTROGEN STIMULATION OF CHOLECYSTOKININ ANDPREPROENKEPHALIN MESSENGER-RNA IN THE RAT HYPOTHALAMUS AND LIMBIC SYSTEM

The neuropeptide cholecystokinin (CCK) is expressed in limbic system a nd hypothalamic nuclei that form a circuit that regulates the display of the female rodent reproductive behavior, lordosis. CCK mRNA and pep tide 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 dete rmine the age at which CCK mRNA expression becomes responsive to estro gen stimulation, by using quantitative in situ hybridization histochem istry. CCK mRNA levels were below the level of detectability within th e circuit during the postnatal period, but increased during the peripu bertal period. Rats were injected with either estradiol benzoate (EB), EB and progesterone, progesterone, or oil, and were killed 48 hours l ater on postnatal day (PND) 15, 20, and 25. Alternate brain sections w ere processed for CCK and preproenkephalin (PPE) mRNA in situ hybridiz ation histochemistry. EB treatment induced CCK mRNA expression in the central portion of the medial preoptic nucleus and posterodorsal media l amygdala at PND 20 and 25, respectively. However, EB treatment incre ased PPE mRNA levels within the nuclei of the circuit at all ages exam ined. Progesterone had neither an independent nor additive effect on t he EB induction of these neuropeptide messages. The estrogenic inducti on 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 lordosi s regulating circuit which are not functional before PND 18-25. (C) 19 98 Wiley-Liss, Inc.