Transcriptional responses of the vasopressin and corticotropin-releasing hormone genes to acute and repeated intraperitoneal hypertonic saline injection in rats

Abstract

The contribution of corticotropin releasing hormone (CRH) and vasopressin (VP) to the adaptation of ACTH responses to chronic stress was studied by analysis of CRH and VP expression in the hypothalamic paraventricular nucleus (PVN) of rats receiving acute or chronic i.p. hypertonic saline injection (ipHS), a stress model in which the HPA axis is not desensitized after repeated stimulation. Repeated ipHS for 14 days had no effect on CRH hnRNA levels but increased CRH mRNA levels by 42.2%. Parallel with preserved plasma corticosterone responses to repeated ipHS, CRH hnRNA responses and CRH mRNA response to the last injection in repeatedly stressed rats were identical to those in naive rats (8.6-fold increase by 15 min, returning to basal level by 1 h). Parvocellular VP hnRNA responses to a single ipHS were slower and more prolonged than for CRH (7.1-, 11.5-, 9.8- and 4.6-fold by 1, 2, 4 and 6 h), and VP mRNA levels increased by 4 h and remained elevated 12 h later. Parvocellular VP hnRNA was at basal levels after 14 days ipHS, but VP mRNA levels remained elevated as during acute stimulation. Despite high basal mRNA levels, VP hnRNA responses to the last repeated ipHS were minor, suggesting increases in mRNA stability. This study shows that conserved pituitary ACTH responsiveness to a homotypical repeated stress is associated with the ability of parvocellular PVN neurons to increase CRH transcription after repeated stimulation.