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. bombe...

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

In the adult castrated male rat, exposure to inescapable, intermittent electroshocks inhibited the pulsatile pattern of luteinizing hormone release and markedly lowered its plasma concentrations. The central administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical ovine CRF residues 9 to 41 reversed the inhibitory action of stress. Neither its peripheral injection, nor the intraventricular injection of the inactive CRF analog des-Glu to Arg ovine CRF was effective. These results suggest that endogenous CRF may mediate some deleterious effects of noxious stimuli on reproduction.

https://science.sciencemag.org/content/sci/231/4738/607.full.pdf

Stress-induced inhibition of reproductive functions: role of endogenous corticotropin-releasing factor

The stress-induced release of ACTH is believed to involve the activation of several humoral and neural pathways, including corticotropin-releasing factor (CRF), catecholamines and vasopressin. The essential role of CRF was supported by our observation that immunoneutralization of this releasing factor significantly lowers plasma ACTH levels of ether-stressed rats. However, the presence of a small but measurable residual ACTH secretion suggested the possible involvement of factors other than CRF in the stress response. We report here that pretreatment with a vasopressin antagonist decreases the plasma ACTH levels of ether-stressed rats in later (10-20 min), but not earlier (0-10 min), phases of ether stress. The ganglionic blocker chlorisondamine, inhibits ACTH release during both phases of the response to ether by 40-60% when used alone, and by 100% when administered with anti-CRF antibody. These results support a role of CRF, catecholamines and vasopressin in mediating ACTH release by ether stress.

Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin

The lateral hypothalamic area revisited: Ingestive behavior

Alternative splicing of RNA transcripts from the calcitonin gene produces mRNAs that encode different polypeptides. While the mRNA encoding calcitonin predominates in thyroidal 'C' cells, calcitonin gene-related peptide (CGRP) mRNA appears to be the major mRNA component in non-thyroid tissue, including brain. The predicted peptide arising from translation of CGRP mRNA has now been identified immunocytochemically throughout the central and peripheral nervous systems. CGRP, a 37-residue peptide, is distributed in brain pathways subserving sensory, motor and autonomic functions. We report here that CGRP acts in the central nervous system to stimulate selectively noradrenergic sympathetic outflow.

Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide.

Bombesin acts within the brain to produce a prompt and sustained hyperglycemia, hyperglucagonemia, and relative or absolute hypoinsulinemia. Bombesin does not decrease plasma glucose turnover. Acute adrenalectomy but not hypophysectomy prevents hyperglycemia and hyperglucagonemia after intracisternal administration of bombesin. Administration of bombesin into the lateral ventricle of awake, unrestrained animals results in elevation of plasma glucose, preceded by a significant increase in plasma epinephrine and no increase in plasma norepinephrine or dopamine. Systemic administration of somatostatin prevents bombesin-induced hyperglycemia and hyperglucagonemia. These data support the conclusion that bombesin acts within the brain to increase sympathetic outflow resulting in increased adrenalmedullary epinephrine secretion, followed by depression of plasma insulin and elevation of plasma glucagon and glucose.

Central nervous system action of bombesin: mechanism to induce hyperglycemia.

The somatostatin analog, des-AA1,2,4,5,12,13-[D-Trp8] somatostatin (ODT8-SS), acts within the central nervous system to suppress the rise in plasma catecholamines associated with a variety of neural stimuli. Insulin-induced hypoglycemia or stress caused significant elevations in plasma catecholamines that were abolished by intracerebroventricular (icv) administration f ODT8-SS. Bombesin, carbachol, or 2-deoxyglucose, injected icv, evoked marked elevations in plasma epinephrine and norepineprine. These effects were also prevented by ODT8-SS given icv. In all experiments, ODT8-SS appeared to be more effective in lowering plasma epinephrine than in lowering plasma norepinephrine. Systemic administration of ODT8-SS was ineffective in lowering plasma catecholamine levels. Native somatostatin given icv produced inconsistent effects on plasma catecholamine levels. These data suggest that the somatostatin analog, ODT8-SS, acts within the central nervous system to modulate sympathetic nervous system activity. It i...

David A. Fisher

Papers

Central nervous system action of bombesin: mechanism to induce hyperglycemia.

Somatostatin analog: plasma catecholamine suppression mediated by the central nervous system.