Glucocorticosteroids up-regulate the expression of cholecystokinin mRNA in the rat paraventricular nucleus

• Published in: Brain research Vol. 877; no. 2; pp. 412 - 423
• Main Authors: Cournil, Isabelle, Lafon, Pierrette, Juaneda, Christian, Ciofi, Philippe, Fournier, Marie-Christine, Sarrieau, Alain, Tramu, Gérard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 22-09-2000
• Subjects: Adrenalectomy - adverse effects; Animals; Cholecystokinin - genetics; Cholecystokinin - metabolism; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Corticosterone feedback; Corticotropin-Releasing Hormone - drug effects; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; CRH mRNA; Feedback - drug effects; Feedback - physiology; Glucocorticoids - metabolism; Glucocorticoids - pharmacology; Hypothalamic–pituitary–adrenal axis; Hypothalamo-Hypophyseal System - cytology; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - metabolism; Male; Neurons - drug effects; Neurons - metabolism; Neuropeptide; Oxytocin - drug effects; Oxytocin - genetics; Oxytocin - metabolism; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Quantitative in situ hybridization; Rats; Rats, Wistar; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology; Endocrine and autonomic regulation; Hypothalamic–pituitary–adrenal axis; Quantitative in situ hybridization; Neuropeptide; Corticosterone feedback; CRH mRNA
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02748-7

Adrenalectomy abolishes corticosteroid feedback onto the hypothalamic–pituitary–adrenal axis. This results in an increased biosynthetic and secretory activity of corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN), sustained in the absence of hormone replacement. In the PVN, cholecystokinin (CCK) is present both in parvicellular CRH-containing and in magnocellular oxytocin (OXY)-containing neurons. We presently studied the glucocorticoid feedback regulation of the expression of cholecystokinin (CCK) mRNA in rats after: (i) adrenalectomy, (ii) sham surgery or (iii) adrenalectomy with corticosterone replacement. Using
35S-labeled CRH and p-CCK cRNA probes and in situ hybridization, CRH and CCK mRNAs were radiolabeled. The total amount of hybridization labeling (integrated density), was quantified in adjacent series of cryosections regularly spaced throughout the PVN. The OXY mRNA detection served to identify PVN magnocellular areas. Adrenalectomy was shown to induce: (i) a 75% increase in CRH mRNA labeling in the PVN, (ii) a concomitant 43% decrease in CCK mRNA labeling but only in the anterior part of the PVN and occurring both in CCK/CRH area (two thirds of it) and CCK/OXY area (one third of it) and (iii) that they were fully reversed by corticosterone replacement. Thus, glucocorticoids that are well known to negatively feedback on CRH expression in parvicellular PVN neurons are also capable of positively regulating CCK expression in anterior PVN neurons, both in parvicellular and magnocellular areas.