Brain receptors for hypothalamic hormones.

Abstract

Angiotensin II and CRF are but two of the several regulatory peptides which exert specific actions in the brain that are complementary with their peripheral effects upon end organs such as the anterior pituitary and adrenal glands. In the pituitary, the two peptides act in a coordinate manner on the corticotroph to regulate ACTH release. In the adrenal gland, angiotensin II receptors are abundant in the zona glomerulosa but are also present in the medulla, where the occurrence of CRF receptors and actions on catecholamine release reveals an additional site at which the two peptides exert related actions, in this case in the peripheral neuroendocrine system. Within the brain, the mapping of AII and CRF binding sites by topical autoradiography has provided new information about the distribution and potential functions of receptors for the two peptides. The central receptors for AII are distributed in a characteristic pattern in brain regions concerned with drinking, regulation of adrenergic function and arterial blood pressure, and control of pituitary hormone secretion. Thus, in addition to its recognized modulatory effects in the peripheral adrenergic system, angiotensin II may be involved in the central control of catecholamine release and action. A central action of AII on the release of regulatory peptides such as vasopressin and CRF, both of which are present in neurones of the paraventricular nucleus, is indicated by the high concentration of AII receptors in this region. Also, the high density of AII receptors in the median eminence suggests that AII modulates the hypothalamic secretion of neuropeptides such as CRF by actions at their site of release, as well as on the cell bodies of neurones responsible for peptide synthesis. The highly localized pattern of AII receptors at numerous specific sites in the brain differs from the more general distribution of many other CNS receptors, and reflects the selective actions of AII on discrete neural systems that subserve precisely integrated functions within the central nervous system. The widespread distribution of CRF receptors, with prominent localization in the cortical and limbic regions, is consistent with the more general neuroregulatory actions of CRF in the brain, and with the presence of immunoreactive CRF in several regions of the brain including the cortex, limbic system, and centers involved in the control of autonomic function. The cortical and limbic receptors are clearly relevant to the effects of centrally administered CRF on both behavioral and visceral responses, with prominent autonomic changes including increased catecholamine release and hypertension.