Corticotropin-Releasing Factor: Actions on the Sympathetic Nervous System and Metabolism*

Abstract

Corticotropin-releasing factor (CRF) injected into the brains of rats produces hyperglycemia and an increase in plasma concentrations of glucagon, epinephrine, and norepinephrine. Neither hypophysectomy nor adrenalectomy prevents CRF-induced hyperglycemia. However, a role of adrenal epinephrine release in mediating CRF-induced hyperglycemia is supported by the finding that the central nervous system-selective somatostatin analog, desAA1,2,4,5,12,13-[D-Trp8]somatostatin, totally prevents the elevation of plasma epinephrine and suppresses the rise of plasma glucose but does not alter the increase in plasma norepinephrine induced by CRF. Pretreatment with the ganglionic blocker chlorisondamine completely prevents the CRF-induced rises in plasma glucose, epinephrine, and norepinephrine. These results demonstrate that CRF acts within the brain to stimulate sympathetic outflow, which results in the development of hyperglycemia. In contrast to other peptides that act within the central nervous system, e.g. bombesin, TRF, and beta-endorphin, whose hyperglycemic actions depend exclusively on adrenal epinephrine secretion, CRF-induced hyperglycemia is secondary to the enhanced secretion of both epinephrine and norepinephrine.

Vital functions of corticotropin-releasing factor (CRF) pathways in maintenance and regulation of energy homeostasis

“…Because core body temperatures were not different between WT and KO mice, these results suggest that through increased IBAT thermogenesis, KO mice lose enough heat, perhaps cutaneous in nature, to distinctly select a warmer environment. This evidence is supportive of our hypothesis that in the absence of CRFR2, increased thermogenesis ensues, possibly by means of elevated CRFR1 activity (17,19).…”

“…Intracerebroventricular (i.c.v.) infusion of CRF elevates sympathetic outflow as measured by increased glucose (17,19), increased brown adipose tissue (BAT) thermogenesis (20), increased uncoupling protein-1 in BAT (21), elevated sympathetic nerve activity to BAT (22,23), increased catecholamines (11,24), and increased corticosterone (11,25). Additionally, i.c.v.…”

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

“…Intracerebroventricular (i.c.v.) injections of CRF increase the firing of locus coeruleus neurons (Valentino and Foote, 1988), increase peripheral sympathetic outflow (Brown et al, 1982) and respiratory rate (Bohemer et al, 1990), and produce proconflict or "anxiogenic-like" effects in a variety of paradigms of emotionality in rodents (Britton et al, 1985;Dunn and File, 1987;Takahashi et al, 1989). Consistent with these observations, central injections of CRF antagonists block the behavioral effects of either exogenously administered CRE stress, or conditioned fear (B&ton et al, 1986;Kalin et al, 1988;Swerdlow et al, 1989;Liang et al, 1992a;Menzaghi et al, 1994).…”

Corticotropin-releasing factor (CRF)-like immunoreactivity in the vertebrate endocrine pancreas.

“…Like other neuropeptides, CRF is widely distributed in extrahypothalamic areas of the brain, determined by both radioimmunoassay (10) and immunocytochemistry (11)(12)(13). In addition to stimulating the release of ACTH and /8-endorphin, CRF has a broad range of pharmacological effects, which include changes in behavior, heart rate, blood pressure, and in blood concentrations of epinephrine, norepinephrine, glucagon, and glucose (14)(15)(16)(17)(18). Thus, CRF appears to be an important regulatory peptide mediating stress-related physiological responses and predictably possessing other, hitherto unsuspected, hormone-or neurotransmitter-like activities.…”