title: Estrogen modulation of opioid and cholecystokinin systems in the limbic-hypothalamic circuit.
abstract: The display of lordosis behavior has been correlated with the estrogen-induced expression of cholecystokinin (CCK) and enkephalin within the limbic-hypothalamic circuit. These neuropeptides have opposing effects on lordosis; for example, in the medial preoptic nucleus, CCK facilitates and opiates inhibit lordosis. Antisense oligodeoxynucleotide blockade of receptor expression indicated that CCK modulates lordosis in the medial preoptic nucleus through the CCK(A)-receptor. Sequence-specific antibodies directed against delta- and mu-opiate receptor proteins labeled fibers in the medial preoptic nucleus. Estrogen treatment of ovariectomized rats or etorphine (a nonselective opiate agonist) treatment altered the appearance of the immunoreactivity from a diffuse pattern to one of distinctly stained mu-opiate receptor immunoreactive cells and varicose fibers in the medial preoptic nucleus. Such a pattern of staining reflects an internalization of mu-opiate receptors following agonist stimulation. This type of internalization has been used as an indication of synaptic activity. The distribution of receptor internalization surrounds the distribution of CCK cells in the medial preoptic nucleus, suggesting that endogenous opioid peptides may modulate estrogen-induced CCK mRNA expression. Interestingly, nonselective and delta-opiate receptor selective antagonists potentiated the estrogen-induced CCK mRNA expression in the medial preoptic nucleus. Together, these results suggest that endogenous opioid peptides may modulate the estrogenic upregulation of CCK mRNA expression and demonstrate an important level of regulation of gene expression in which synaptic activity modifies hormonal input.
authors.affiliation: Department of Neurobiology, Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Micevych
authors.forename: C B
authors.initials: CB
authors.lastname: Eckersell
authors.forename: N
authors.initials: N
authors.lastname: Brecha
authors.forename: K L
authors.initials: KL
authors.lastname: Holland
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000096:biosynthesis / Q000502:physiology*; D004745:Enkephalins / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000502:physiology*; D008032:Limbic System / Q000502:physiology*; D008297:Male; D016376:Oligonucleotides, Antisense; D011187:Posture; D051381:Rats; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology; D012726:Sexual Behavior, Animal; D014158:Transcription, Genetic
chemical_list: D004745:Enkephalins; D016376:Oligonucleotides, Antisense; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D011957:Receptors, Opioid; D002766:Cholecystokinin