Lack of correlation between immunoreactive corticotropin-releasing factor concentration profiles in...

Abstract Corticotropin-releasing factor (CRF-41) is the primary mediator of adrenocorticotropin secretion from the adenohypophysis. This 41-amino-acid peptide is synthesized in perikarya of the paraventricular nuclei, transported to nerve terminals in the external zone of the median eminence and released into the hypophysial-portal circulation. It is also synthesized in multiple extrahypothalamic and peripheral sites. In addition, immunoreactive (ir) CRF-41 is present in the systemic circulation, raising the possibility that systemic measurements might provide a useful index of hypothalamic irCRF-41 secretion. This hypothesis was tested in several rat models. Neither bilateral destruction of hypothalamic irCRF-41 producing perikarya, nor infundibular stalk transection altered peripheral plasma irCRF-41 concentration. Furthermore, central administration of norepinephrine, an agent previously shown to evoke irCRF-41 secretion into the portal circulation, was without effect on peripheral irCRF-41 concentration. Finally, while increased irCRF-41 levels in both the hypophysial-portal and the peripheral circulation were associated with nitroprusside-induced hypotension, bilateral paraventricular nuclei lesions blocked irCRF-41 secretion into the hypophysial-portal circulation without blunting the rise observed in the peripheral circulation. The source of peripheral irCRF-41 remains undetermined; however, the adrenals may be excluded as bilateral adrenalectomy failed to alter circulating irCRF-41 levels. Therefore, our observations do not support the concept that peripheral irCRF-41 levels provide a useful index of hypothalamic secretion of this peptide into the hypophysial-portal circulation under the conditions tested.