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Vasopressinergic Control of Pituitary Adrenocorticotropin Secretion Comes of Age

This article summarizes the importance of arginine vasopressin (AVP) in the control of adrenocorticotropin (ACTH) secretion, with special reference to interactions with corticotropin releasing factor (CRF-41), glucocorticoids, and the purported corticotropin release inhibiting peptide atriopeptin. AVP that participates in the regulation of ACTH release at the pituitary level is produced in two main groups of neurons in the hypothalamus: parvicellular cells in the paraventricular nucleus, which also produce CRF-41, and magnocellular neurons in the supraoptic and paraventricular nuclei. The role of the latter in anterior pituitary hormone release has been debated for many years. Evidence generated in the last 5 years shows quite convincingly that AVP released by magnocellular neurons is, in fact, also involved in the control of ACTH. Nevertheless, it is clear that corticotrope cells require CRF-41 to maintain their capacity to secrete ACTH. This is at least due partly to the fact that AVP does not increase proopiomelanocortin mRNA transcription, while CRF-41 is a potent inducer of this gene. New developments in the area of corticotrope cell physiology are discussed, highlighting evidence for dual ACTH secreting pathways in anterior pituitary cells, which may be controlled separately by AVP and CRF-41. Evidence for interactions between ACTH secretagogues and peptidergic as well as glucocorticoid inhibitors of ACTH secretion is reviewed to demonstrate that an important aspect of AVP/CRF-41 dualism may be associated with the ability of the secretagogues to selectively modulate the efficacy of inhibitory factors. Finally, by citing examples from physiological studies on the regulation of ACTH secretion, it is shown how the multicomponent hypothalamic regulatory system operates, emphasizing the considerable signal integrating role of the adenohypophysial corticotrope cell.