Corticotropin‐releasing Factor in the Adrenal Medulla
ABSTRACT Immunoreactive and bioactive corticotropin-releasing factor has been identified in the adrenal gland of dogs, rats and humans. Radioimmunoassay and immunohistochemical experiments have clearly demonstrated that localization of the peptide is confined to the adrenal medulla. CRF-containing cells have a characteristic appearance and are often found in close association with blood vessels. Electron microscopic studies suggest that CRF is secreted at blood vessels within the adrenal medullary vasculature. CRF has also been identified in pheochromocytomas. The amount of the peptide made by such tumors is highly variable as the CRF content of pheochromocytomas may be 20 to 100 times higher or lower than that of normal adrenal tissue. The pathophysiological importance of CRF in pheochromocytomas is unknown. Excessive secretion of the peptide into the peripheral circulation may cause prolonged activation of the pituitary adrenal axis. The peptide may also act within the tumor, although its role remains obscure. Studies on chronically cannulated, awake dogs have shown that CRF is secreted into adrenal venous blood. A gradient exists between adrenal venous and peripheral arterial blood, as CRF is undetectable peripherally under resting conditions. Hemorrhage, a hemodynamic stimulus known to activate a sympathetic adrenal response, increases the CRF secretory rate. The time course of CRF secretion in response to this stimulus parallels that of epinephrine secretion. The physiological significance of adrenal medullary CRF remains to be determined. Although CRF has been shown to affect catecholamine secretion, the peptide appears to be only a weak secretagogue for catecholamines. We suggest that CRF may affect local blood flow within the adrenal medulla and may modify catecholamine secretory rates via this mechanism. The localization of CRF cells in close apposition to blood vessels supports this hypothesis.
- SourceAvailable from: Mark O. Huising
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- "The adrenal medulla in particular produces and contains many neurotransmitters and peptide hormones other than CRF, such as neuropeptide Y, serotonin (5-HT), and vasoactive intestinal peptide; the presence has been established, but the functions are incompletely understood (Nussdorfer 1996, Ehrhart-Bornstein et al. 1998). CRF is found exclusively in a subpopulation of medullary chromaffin cells (Hashimoto et al. 1984, Suda et al. 1984, Bruhn et al. 1987a,b, Minamino et al. 1988). Moreover, direct effects of CRF, independent of HPA-axis activation, have been demonstrated on adrenocortical steroid release (Bornstein et al. 1990, Jones & Edwards 1992, van Oers et al. 1992, Nussdorfer 1996). "
ABSTRACT: Corticotropin-releasing factor (CRF) plays a central role in the regulation of the stress axis. In mammals, CRF as well as its receptors and its CRF-binding protein (CRF-BP) are expressed in a variety of organs and tissues outside the central nervous system. One of these extrahypothalamic sites is the adrenal gland, where the paracrine actions of adrenal CRF influence cortical steroidogenesis and adrenal blood flow. Although the central role of CRF signaling in the initiation and regulation of the stress response has now been established throughout vertebrates, information about the possible peripheral presence of CRF in earlier vertebrate lineages is scant. We established the expression of CRF, CRF-BP, and the CRF receptor 1 in a panel of peripheral organs of common carp (Cyprinus carpio). Out of all the peripheral organs tested, CRF and CRF-BP are most abundantly expressed in the carp head kidney, the fish equivalent of the mammalian adrenal gland. This expression localizes to chromaffin cells. Furthermore, detectable quantities of CRF are released from the intact head kidney following in vitro stimulation with 8-bromo-cAMP in a superfusion setup. The presence of CRF and CRF-BP within the chromaffin compartment of the head kidney suggests that a pathway homologous to the mammalian intra-adrenal CRF system is present in the head kidney of fish. It follows that such a system to locally fine-tune the outcome of the centrally initiated stress response has been an integral part of the vertebrate endocrine system since the common ancestor of teleostean fishes and mammals.Journal of Endocrinology 07/2007; 193(3):349-57. DOI:10.1677/JOE-07-0070 · 3.72 Impact Factor
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ABSTRACT: Over the past twenty years, each of the five major hypothalamic releasing or release-inhibiting hormones has been sequenced and its gene structure determined. With the use of molecular biological techniques, such as in situ hybridization, Northern blot analysis or gene constructs for in vitro or in vivo transfection studies—together with “traditional’ neuroendocrinological techniques, such as immunocytochemistry, radio-immunoassay and portal vessel cannulation—investigators have been able to address major issues in neuroendocrine regulation. Several common themes have emerged: messenger RNA expression is uniformly present in neurons that are immunopositive for the specific hypothalamic hormone. Steady state RNA levels within the hypophysiotropic neuron groups are either increased or reduced by changes in specific target hormones that conform to predictions based on previous physiological data. Regulation by the requisite peripheral hormone is exquisitely anatomically specific and is not evident in extrahypophysiotropic regions. Determining the receptor or genetic basis of this specificity is a major focus of current research. Clarifying the apparently lesser role of afferent neural pathways to the hypothalamus in regulating releasing hormone mRNA levels is also an important challenge.Clinically, the measurement of levels of releasing hormones in the peripheral circulation appears to be of limited usefulness, except in rare cases of ectopic GRH or CRH secretion. For diagnostic purposes, each of the releasing hormones has specific utility in amplifying the release and measurement of pituitary hormones, both to clarify the overall physiological activity of the hypothalamic—pituitary—target hormones axis and to further define the anatomic locus of any underlying disturbance. The usefulness of somatostatin as a diagnostic tool is presently limited, but the development of SS receptor antagonists might have significant impact in future clinical investigation.The molecular mechanisms of action of the hypothalamic hormones have been separated into those whose reeptor-effector function is mediated by the cAMP-adenylate cyclase pathway(s), GRH and CRH, and those working through the phosphoinositide-protein kinase C cascade, GnRH and TRH. Each of the hormone receptors is coupled to intermediary G proteins, somatostatin uniquely to the inhibitory subclass. The mechanisms responsible for sensitization (priming) or desensitization are not fully understood but are presumably related to receptor down regulation and protein phosphorylation. Cloning of the genes of the hypothalamic hormone receptors will provide an important link in the molecular biology of their signal transduction.Finally, advances in our understanding of the gene transcription, secretion and signal transduction of the hypothalamic hormones will provide a progressively more sophisticated basis for their therapeutic applications. Currently GnRH, and GnRH and somatostatin analogues have the most clearly established therapeutic usefulness. Advances in administration techniques or analogue or antagonist development may permit further therapeutic uses of TRH, GRH, and CRH—not only in hypothalamic—pituitary disease but also in other settings, such as neurological and psychiatric disease, chronic stress, and ageing.Baillière s Clinical Endocrinology and Metabolism 11/1988; 2(4-2):835-868. DOI:10.1016/S0950-351X(88)80021-1
- Annals of the New York Academy of Sciences 02/1990; 597(1 Neurobiology):71-80. DOI:10.1111/j.1749-6632.1990.tb16159.x · 4.38 Impact Factor