Influence of steroids on the hypothalamic corticotropin-releasing factor and preproenkephalin mRNA responses to stress

Abstract

We have used in situ hybridization histochemistry to investigate the influence of both circulating corticosteroids and the stress paradigm of i.p. hypertonic saline on the levels of mRNAs encoding corticotropin-releasing factor (CRF) and preproenkephalin in parvocellular neurons of the rat hypothalamus. Stress increased both CRF and preproenkephalin mRNAs, whereas adrenalectomy increased only CRF mRNA. After adrenalectomy, even when CRF mRNA had reached peak levels, stress still further increased CRF mRNA and caused an exaggerated rise in preproenkephalin mRNA. Dexamethasone administration in the fast or intermediate-feedback time domains had no effect on CRF or preproenkephalin mRNA responses to stress; however, when administered over a longer period of time in the slow-feedback time domain dexamethasone reduced basal CRF mRNA levels and the stress-stimulated levels of CRF and preproenkephalin mRNA. These results show that different stimuli to the parvocellular paraventricular hypothalamus differentially regulate CRF transcript levels. Furthermore, in spite of the lack of any detectable effect of changes in circulating glucocorticoid levels on basal levels of preproenkephalin mRNA, glucocorticoids markedly alter the preproenkephalin mRNA response to stress.