title: The relationship between adrenal vascular events and steroid secretion: the role of mast cells and endothelin.
abstract: The actions of ACTH on the adrenal cortex are known to be 2-fold. In addition to increased steroidogenesis, ACTH also causes marked vasodilation, reflected by an increased rate of blood flow through the gland. Our studies, using the in situ isolated perfused rat adrenal preparation, have shown that zona fasciculata function and corticosterone secretion are closely related to vascular events, with an increase in perfusion medium flow rate causing an increase in corticosterone secretion, in the absence of any known stimulant. These observations give rise to two important questions: how does ACTH stimulate blood flow; and how does increased blood (or perfusion medium) flow stimulate steroidogenesis? Addressing the first question, we have recently identified mast cells in the adrenal capsule, and shown that Compound 48/80, a mast cell degranulator, mimics the actions of ACTH on adrenal blood flow and corticosterone secretion. We have also demonstrated an inhibition of the adrenal vascular response to ACTH in the presence of disodium cromoglycate, which prevents mast cell degranulation. We conclude, therefore, that ACTH stimulates adrenal blood flow by its actions on mast cells in the adrenal capsule. Addressing the second question, we looked at the role of endothelin in the rat adrenal cortex. Endothelin 1, 2 and 3 caused significant stimulation of steroid secretion by collagenase dispersed cells from both the zona glomerulosa and the zona fasciculata. A sensitive response was seen, with significant stimulation at an endothelin concentration of 10(-13) mol/l or lower. Endothelin secretion by the in situ isolated perfused rat adrenal gland was measured using the Amersham assay kit. Administration of ACTH (300 fmol) caused an increase in the rate of immunoreactive endothelin secretion, from an average of 28.7 +/- 2.6 to 52.6 +/- 6 fmol/10 min (P less than 0.01, n = 5). An increase in immunoreactive endothelin secretion was also seen in response to histamine, an adrenal vasodilator, which stimulates corticosterone secretion in the intact gland, but has no effect on collagenase-dispersed cells. From these data we conclude that endothelin may mediate the effects of vasodilation on corticosterone secretion, and this mechanism may explain some of the differences in response characteristics between the intact gland and dispersed cells.
authors.affiliation: Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, London, England.
authors.forename: J P
authors.initials: JP
authors.lastname: Hinson
authors.forename: G P
authors.initials: GP
authors.lastname: Vinson
authors.forename: S
authors.initials: S
authors.lastname: Kapas
authors.forename: R
authors.initials: R
authors.lastname: Teja
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D016232:Endothelins / Q000502:physiology*; D066298:In Vitro Techniques; D008407:Mast Cells / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation; D015383:Zona Fasciculata / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D016232:Endothelins; D003189:p-Methoxy-N-methylphenethylamine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone