Norepinephrine-induced CRH and AVP gene transcription within the hypothalamus: differential regulation by corticosterone

Abstract

We have previously demonstrated that microinjection of norepinephrine (NE) into the paraventricular nucleus of the hypothalamus (PVN) of conscious rats elicits a marked increase in CRH gene transcription, indicated by CRH hnRNA levels, without changing AVP hnRNA levels. We hypothesized that this differential response is due to differential sensitivity of AVP and CRH gene transcription to the inhibitory effects of the NE-induced rise in corticosterone. In the current study, we used animals that had been adrenalectomized and implanted with a subcutaneous corticosterone pellet (ADX/B) which prevented the NE-induced rise in corticosterone levels. NE (50 nmol) or artificial CSF was injected into the PVN of conscious rats, which had undergone either sham-operation (SHAM) or ADX/B 1 week earlier. CRH and AVP hnRNA levels were semi-quantitated by in situ hybridization using intron-specific riboprobes. In both SHAM and ADX/B animals, CRH hnRNA levels were significantly elevated at the 15 min time-point and returned to basal levels by 120 min. At 15 min, the magnitude of the CRH hnRNA response was only slightly greater in the ADX/B group than SHAM. In contrast, changes in medial parvocellular PVN AVP hnRNA levels in the ADX/B group were significantly greater than the changes observed in the SHAM group, at both the 15 and 120 min time-points. These results suggest that corticosterone has a greater impact on the transcriptional regulation of AVP than CRH, suggesting important differences and distinct roles of these secretagogues in the regulation of the hypothalamic–pituitary–adrenal axis.