Effects Of Recombinant Murine Leptin[1-147] And Leptin Fragment 116-130 On Steroid Secretion And Proliferative Activity Of The Regenerating Rat Adrenal Cortex

Abstract

Leptin, the product of the oh gene, is a hormone mainly secreted by the adipose tissue, which acts through specific receptors (Ob-R) widely distributed in the body tissues Ob-Rs are present in the mammalian hypothalamo-pituitary-adrenal axis, and evidence indicates that leptin regulates adrenocortical secretion Moreover, leptin is known to act as a growth promoting factor in some tissues, including the endocrine ovary. We have investigated the effects of three subcutaneous injections of 2 nmol/100 g of native murine leptin[1–147] and of its biologically active fragment 116–130 on the secretory and proliferative activity of the regenerating rat adrenal cortex Leptin[1–147] increased plasma aldosterone concentration at day 8 and plasma corticosterone concentration (PBC) at day 5 of regeneration, without affecting mitotic index. In contrast, leptin[116–130] lowered PBC and mitotic index at both times of adrenal regeneration. In light of the fact that adrenal regeneration is at least in part dependent on the pituitary ACTH, we conclude that (i) native leptin moderately stimulates steroid secretion, acting directly on the adrenal cortex, through signaling mechanisms other than those involved in the ACTH action, (ii) native leptin is unable to enhance the proliferative activity of regenerating adrenals, which conceivably is maximally stimulated by ACTH; (iii) leptin[1–147] and leptin[116–130] differently interact with Ob-Rs or interact with different receptors; and (iv) leptin[116–130] inhibits the signaling pathways mediating both the secretagogue effect of native leptin and the proliferogenic effect of ACTH.