Acute in vivo effects of leptin and leptin fragments on corticosteroid hormone secretion and entero-insular axis in the rat.

Leptin is a 147-amino acid adipose tissue-secreted hormone, which acts via several subtypes of receptors, the main and better known variants of which are named Ob-Ra and Ob-Rb. Structure-activity relationship studies pointed out the importance of the N-terminal and C-terminal amino-acid sequences 22-115 and 116-166, respectively, for the biological and receptor binding activities of leptin. Evidence has been provided that leptin affects corticosteroid-hormone and insulin secretion, and therefore we have investigated in the rat the expression of leptin receptor expression in adrenal cortex and pancreatic islets, as well as the effects of the acute treatment with leptin and leptin fragments 150-167, 138-167, 93-105, 22-56 and 26-39 on the plasma concentrations of aldosterone, corticosterone, insulin and glucagon. Reverse transcription-polymerase chain reaction showed the expression of both Ob-Ra and Ob-Rb mRNAs in adrenal cortex and pancreatic islets, the Ob-Rb expression in pancreas being 2-fold higher than in adrenals. Radioimmuno assay demonstrated that leptin enhanced plasma aldosterone and corticosterone concentrations, decreased plasma insulin concentration, and did not significantly affect glucagon plasma concentration. All leptin fragments tested exerted a corticosteroid-hormone secretagogue action, while only leptin fragments 116-130, 138-167 and 93-105 elicited a sizeable insulin antisecretagogue effect. Taken together these findings suggest that: i) the in vivo acute stimulating effect of leptin on adrenocortical hormone secretion is not connected to specific sequences of its molecule, while the insulinostatic effect is probably mediated by the sequence 93-105; and ii) the secretagogue and antisecretagogue effect of leptin are prevalently mediated by Ob-Ra and Ob-Rb, respectively.