Regulation of corticotropin-releasing hormone receptors and hypothalamic pituitary adrenal axis responsiveness during...

The relationship between pituitary corticotropin-releasing hormone (CRH) receptor changes and corticotrope responsiveness was studied during chronic cold stress. Exposure of rats to 4°C caused a gradual increase in plasma adrenocorticotropic hormone (ACTH), reaching 3-fold over the basal levels by 6 h (P< 0.005), followed by a reduction to levels only 1.3-fold over basal by 60 h. Plasma corticosterone was significantly increased after 1 h (P<0.005) and remained elevated for up to the 60 h cold exposure (P < 0.005). No significant changes in plasma thyroid-stimulating hormone, prolactin, growth hormone or vasopressin were observed at 60 h of cold exposure. CRH receptor concentration in the anterior pituitary was unchanged after 18 or 60 h cold stress, whereas in neurointermediate lobe membranes was markedly elevated. Autoradiographic analysis of pituitary CRH receptors confirmed that the increase in CRH binding was confined to the intermediate pituitary. CRH receptor levels in membranes from two brain areas, frontal cortex and amygdala, were unchanged following 60 h cold stress. The areas under the curve for the plasma ACTH and corticosterone levels following an injection of 10μg/kg ovine CRH in conscious rats, were of similar magnitude in control and 60 h cold exposed rats. Plasma ACTH responses to ether stress were significantly higher in rats exposed to cold for 60 h than in controls. In the intermediate pituitary, basal ß-endorphin/lipotropin release from isolated intermediate pituitary cells was significantly lower in cold stressed rats, and despite the increase in CRH receptors CRH-stimulated values were not higher than in controls. Following 60 h cold exposure, immunoreactive CRH content was decreased in neurointermediate pituitary extracts, while it was slightly increased in the median eminence. Exposure to ether for 5 min resulted in a significant decrease in immunoreactive CRH in the median eminence of cold stressed rats, but not in the controls. The data show a lack of correlation between changes in CRH receptor levels and responsiveness of the corticotrope in the anterior and intermediate pituitary lobes. This suggests that postreceptor events and interaction of CRH with other regulators of ACTH secretion are more likely to account for the changes in pituitary responsiveness during chronic stress.