Differential 5-HT-mediated regulation of stress-induced activation of proopiomelanocortin (POMC) gene expression in the anterior and intermediate lobe of the pituitary in male rats.

The purpose of the present study was to examine the role of 5-hydroxytryptamine (5-HT) neurons in mediating the effects of stress on proopiomelanocortin (POMC) gene expression in the anterior and intermediate lobes of the pituitary gland. To this aim, the effects of 5-HT depletion induced by administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 200 microg/rat; i.c.v.; 7 days) were investigated on POMC mRNA levels in the anterior and intermediate lobe of control and restraint-stressed rats. Three hours after brief exposure to diethyl ether (2 min) followed by 60 min of restraint stress increased POMC mRNA levels in the anterior and intermediate lobe of the pituitary. 5,7-DHT neurotoxic lesion, which resulted in a marked depletion of 5-HT (below the level of sensitivity of the neurochemical assay, 6 pg/sample) but not of dopamine or norepinephrine concentrations in the periventricular nucleus of the hypothalamus, had no effect on basal POMC mRNA levels in the anterior or intermediate lobe of the pituitary. However, 5-HT depletion further increased POMC mRNA levels in the anterior pituitary and completely blocked POMC mRNA level enhancement induced in the intermediate lobe of stressed rats. These results suggest a possible inhibitory 5-HT tone on POMC gene expression in the anterior pituitary and a stimulatory 5-HT tone in the intermediate lobe of the pituitary under these experimental conditions of stress. It appears, therefore, that 5-HT exerts a differential regulation of stress-induced activation of POMC gene expression in the anterior and intermediate lobes of the pituitary in male rats.