NEURAL REGULATION OF CORTICOTROPIN-RELEASING HORMONE (CRH) AND CRH RECEPTOR MESSENGER-RNA IN THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS IN THE RAT

The role of afferent innervation to the hypothalamic paraventricular n ucleus (PVN) on CRH mRNA and CRH receptor mRNA levels was studied in c ontrol and stressed rats. Groups of rats were subjected to unilateral transection of the stria terminalis (ST), the medial forebrain bundle at the rostral hypothalamic level (RMFB), or the lower brainstem throu gh the medulla oblongata between the obex and the locus coeruleus (CBs ). Twelve days after surgery, each group of rats was further divided i nto controls (basal conditions) and stressed (1 h immobilization), bef ore collecting brains for mRNA analysis by in situ hybridization histo chemistry. While ST and RMFB cuts had no effect on basal CRH mRNA leve ls in the PVN, CBs cut decreased CRH mRNA in the PVN ipsilaterally to the knife cut but it was without effect on the contralateral side (-40 % and -37% vs contralateral and sham-operated, respectively, P<0.01). Acute stress (rats were killed 3 h after immobilization)increased CRH mRNA levels by about 30% bilaterally, an effect which was unchanged by any of the three hemisections. Under basal conditions, CRH receptor m RNA levels in the PVN were indistinguishable from the surrounding area s in sham-operated controls, ST and RMFB operated rats. However, brain stem hemisection resulted in clear expression of CRH receptor mRNA in areas consistent with the dorsal, medial-ventral and lateral parvicell ular subdivisions of the PVN, ipsilateral to the transection. CRH neur ons in these subdivisions project to the lower brainstem and the spina l cord. Expression of CRH receptor mRNA in the medial-dorsal and anter ior parvicellular divisions (CRH neurons with median eminence projecti ons) was not affected by CBs cut. In these subdivisions, immobilizatio n stress markedly increased CRH receptor mRNA levels but it did not in fluence CBs cut-induced CRH receptor expression, ST and RMFB hemisecti ons were without effect on PVN CRH receptor mRNA levels under basal or stress conditions. Oxytocin (OT) and vasopressin (VP) mRNA levels in the magnocellular subdivision of the PVN were unchanged after immobili zation, or following ST, RMFB or CBs cuts, whereas OT mRNA in the medi al-ventral and caudal parvicellular subdivisions was decreased by 52% after CBs cut. The data demonstrate that: 1) basal CRH mRNA levels in the PVN are under tonic stimulatory influence of the lower brainstem ( and/or spinal cord) afferents; 2) CRH receptor mRNA expression in PVN subdivisions (pituitary vs lower brainstem/spinal cord projecting neur ons) is under different control mechanisms, and 3) immobilization-indu ced changes in CRH mRNA and CRH receptor mRNA levels are mediated eith er by neural inputs from brain areas other than those investigated her e, or by humoral factors.