Evidence for a role of endogenous corticotropin-releasing factor in cold, ether, immobilization, and traumatic stress.

Abstract

The role of corticotropin-releasing factor (CRF) in four model stresses (cold, ether, immobilization, and trauma) was examined in the guinea pig by using passive immunoneutralization with anti-CRF antiserum. Plasma corticotropin levels were measured at various times after exposure to stress, and groups treated with CRF antiserum were compared with those treated with normal rabbit serum. Of the four stresses tested, ether had the most pronounced effect on corticotropin secretion. Treatment with anti-CRF inhibited most of the ether-induced corticotropin secretory response, the difference between the normal serum-and the anti-CRF antiserum-treated groups being significant at 5 and 10 min (P < 0.01). Corticotropin responses to cold stress in the two groups differed at the 0.05 level of significance at 10 and 20 min. After administration of trauma (leg fracture), a statistically significant difference (P < 0.01) between the two groups also was evident, albeit only at 20 min. During immobilization, corticotropin levels differed significantly from control only in the normal serum-treated group but not in the anti-CRF-treated group. These findings show that CRF antiserum was effective in reducing corticotropin levels, indicating that CRF has an important role in mediating corticotropin response to stress. The fact that neutralization was incomplete might be due to an inability of the antiserum to sufficiently neutralize the endogenous CRF or, more likely, reflects the contribution of additional mediators, notably catecholamines and vasopressin, of corticotropin release upon stress.Corticotropin-releasing factor (CRF) has long been postulated to have a physiological role in modulating corticotropin (adrenocorticotropic hormone, ACTH) and l3-endorphin secretion (1-3). Recent elegant studies in the rat (4) strongly imply that CRF and/or an endogenous peptide immunologically related to CRF has a physiologic role in the maintenance of elevated levels of circulating corticotropin in adrenalectomized rats and in the activation of the pituitary-adrenal axis due to ether stress. However, diverse stresses differ considerably in their pathophysiology, sequelae, and underlying neural control of corticotropin secretion (5-20). There-fore, these studies were undertaken utilizing a similar in vivo paradigm in the guinea pig to ascertain whether CRF performs an analogous role in other forms of stress. The results of the passive immunoneutralization approach (4, 21), which in this instance entails intravenous administration of a potent antibody against ovine CRF (oCRF) to the guinea pig before exposure to cold (6,15,19), trauma (8, 9), immobilization (14, 15, 17), or ether stress (5, 10, 11, 18), suggest that an endogenous CRF-like peptide does play a physiological role in the regulation of corticotropin in these model stresses. METHODSA polyclonal antibody (hereafter referred to as anti-CRF) from rabbit 471 was used for the in vivo neutralization studies. It was prepared by the same methods used previously to raise antiserum fo...

Suppression of hypothalamic-pituitary-adrenal axis responsiveness to stress in a rat model of acute cholestasis.

“…The increase in plasma ACTH after exposure to saturated ether vapor, a well-described systemic stressor in rats ( 13) (21 ). Thus, the diminished hypothalamic CRF content in BDR rats does not appear to be attributable to chronic stress per se.…”

“…Ether vapor has been shown to activate the HPA axis in part by stimulating CRF release from the hypothalamus ( 13).…”

Neonatal endotoxin exposure alters the development of the hypothalamic- pituitary-adrenal axis: early illness and later responsivity to stress

“…Indeed, the differences in the terminal pools of CRH and AVP suggest that endotoxin-treated and control animals would differ in stressors mediated by either secretagogue. Note, pituitary ACTH responses to restraint stress are mediated by dynamic variations in both CRH and AVP (Linton et al, 1985;Nakane et al, 1985).…”

Prenatal Malnutrition-Induced Changes in Blood Pressure

“…Noxious or offensive odors are well validated as stressors in this species. 17,18 Hypothesis 2 was that prenatally malnourished rats would exhibit a greater elevation of blood pressure than the well-nourished controls on exposure to stress. Contrary to hypothesis 1, prenatal malnutrition brought about a small but significant elevation of DBP during the dark phase of the cycle.…”