Endocrine Abstracts

Adrenal insufficiency can result in severe hyponatremia due to inappropriate high plasma vasopressin (pAVP). To elucidate the glucocorticoid AVP feedback we monitored thirsting of 12 male volunteers without and after on or five days of prednisolone (30 mg/d). Although prednisolone suppressed pAVP below 0.2 pg/ml the rise in plasma osmolality during thirsting was not influenced by prednisolone. Independent of exogenous glucocorticoid thirsting resulted in higher urine osmolality and decreased urine volume. Although pAVP was extremely low there was no difference in urinary secretion of aquaporin-2 (AQP2). Exogenous stimulation of the AVP V2 receptor by 4 μg desmopressin resulted in normal renal response with increased urine osmolality and decreased urine volume. The V2 agonist induced a significant increase of urinary AQP2 secretion. This increase is independent of prednisolone intake and suggests that AVP is able to act normally on the translocation of the water channel AQP2 in the principal cells of the collecting duct, compatible with our data of a prednisolone unrestricted rise in urinary cAMP excretion after desmopressin injection. Evidence has been reported that both secretion of atrial natriuretic peptide (ANP) and synthesis of prostaglandin E2 (PGE2) are influenced by the action of glucocorticoids and that they may modulate renal AVP action. In this study urinary excretion of PGE2 was not influenced by prednisolone intake. Plasma ANP concentration were higher during prednisolone treatment. An AVP independent effect of elevated ANP on AQP2 translocation would be compatible with the reported phosphorylation of AQP2 at Ser256 by protein kinase G (PKG) and subsequent AQP2 membrane translocation.

The experiments show a strong feedback inhibition of the glucocorticoid prednisolone on AVP secretion. Preserved renal water reabsorption after thirsting in the presence of prednisolone suggests an AVP independent mechanism that may be influenced by higher ANP plasma concentrations.