Vasopressin stimulates steroid secretion in human adrenal glands: comparison with angiotensin-II effect.

Abstract

Autoradiographic experiments using iodinated vasopressin analog revealed the presence of specific vasopressin-binding sites in the human adrenal cortex (zona glomerulosa and zona fasciculata). These receptors exhibited a good affinity for arginine vasopressin (3.3 nM), with classical V1a pharmacology and densities of 65 and 135 fmol/mg protein-enriched membranes from zona glomerulosa and fasciculata, respectively. Vasopressin receptors present in both glomerulosa and fasciculata cell-enriched primary cultures were coupled to phospholipase C (ED50, 0.9 and 1.8 nM; maximal stimulation, 4.3- and 5.8-fold, respectively). Vasopressin also stimulated an increase in intracellular calcium through at least two distinct mechanisms: the mobilization of intracellular pools via vasopressin-stimulated inositol phosphate accumulation and the activation of calcium influx. In glomerulosa cell-enriched primary cultures, vasopressin increased aldosterone secretion (ED50, 0.4 nM; maximal stimulation, 2.5-fold) and was found to be as potent as angiotensin-II in stimulating aldosterone secretion, phosphoinositide turnover, and calcium mobilization. In fasciculata cells, vasopressin and angiotensin-II were also able to stimulate cortisol secretion and inositol phosphate accumulation. Moreover, perifusion experiments demonstrated that vasopressin was released from the adrenal medulla. Together, these results indicate that vasopressin can be considered a potent paracrine modulator of adrenal steroid secretion in man.

Role of Ca2+ in the action of adrenocorticotropin in cultured human adrenal glomerulosa cells.

“…In contrast to that observed with AVP (or other Ca 2ϩ -mobilizing hormones) (5,32), this increase does not exhibit transient spikes. The amplitude of the increase in [Ca 2ϩ ] i is similar to that observed during the plateau phase of AVP and remains sustained.…”

“…Primary cultures of human glomerulosa cells loaded with Fura 2 were stimulated with either 100 nM ACTH or, as a control, with 100 nM AVP, a potent activator of phospholipase C in these cells (5). Fig.…”

“…Potassium ion, angiotensin II (Ang II), and adrenocorticotropin hormone, as well as epinephrine, serotonin, endothelin, ␣ -MSH, and vasopressin are all known to be potent secretagogues (1)(2)(3)(4)(5)(6)(7). Preliminary in vitro studies, conducted either in human adrenocortical cells (5,8,9) or with NCI-H295 adrenocortical carcinoma cells (10), indicate that ACTH (5,8,9) or dibutyryl cAMP (10) are as potent as Ang II in stimulating aldosterone secretion; however, there are no studies concerning the early events of ACTH action.…”

“…After removal, glands were kept on ice in McCoy's medium and transported within 4 h to the laboratory. Glands were processed as previously described (5). Briefly, adrenal glands were cleansed of fat and cut into four or five flat sections.…”

Structure and conformation of Arg8 vasopressin modified analogs

“…[1 -3] AVP is also involved peripherally, e.g. in the regulation of insulin and glucagon release by the pancreas; [4,5] steroid and catecholamine secretion by the adrenals; [6] glycogenolysis in the liver; [7] and the release of atrial natriuteric factor from the heart. [8] Centrally, AVP has multiple actions, including the regulation of memory, synaptic transmission, body temperature, pain, and depression.…”