TY - JOUR AB - Insulin-like growth factor (IGF)-I is a ubiquitously synthesized peptide that, along with IGF-II, acts via the IGF-R type I receptor. IGF-I and its receptor are expressed in the adrenal gland of humans and bovines, the secretion of which they seem to stimulate. As in humans and cows, the main glucocorticoid hormone secreted by guinea-pig adrenals is cortisol, and hence we have studied the adrenocortical effects of IGF-I in this species. In vivo experiments showed that prolonged IGF-I administration raised the plasma concentration of cortisol in both normal and dexamethasone/captopril-treated guinea pigs, thereby ruling out the possibility that IGF-I may act by activating the hypothalamic-pituitary-adrenal axis and the renin-angiotensin system. In vitro experiments demonstrated that IGF-I enhanced basal, but not maximally agonist [ACTH and angiotensin-II (Ang-II)]-stimulated, cortisol secretion from freshly dispersed guinea-pig inner adrenocortical cells. The IGF-I immuno-neutralization suppressed the IGF-I secretagogue effect, without altering the cortisol response to both ACTH and Ang-II. IGF-I raised cyclic-AMP and inositol triphosphate release from dispersed guinea-pig cells, and the effect was reversed by the adenylate cyclase inhibitor SQ-22536 and the phospholipase-C (PLC) inhibitor U-73122. SQ-22536, U-73122, the protein kinase (PK) A inhibitor H-89 and the PKC inhibitor calphostin-C decreased by approximately 50% the cortisol response of dispersed cells to IGF-I, and the combined exposure to SQ-22536 and U-73122 abolished it. We conclude that IGF-I stimulates glucocorticoid secretion from guinea-pig adrenocortical cells, acting via selective receptors coupled to both the adenylate cyclase/PKA- and PLC/PKC-dependent signaling cascades. AD - Department of Zoology, Ranchi University, Ranchi 834008, India null AU - Raha,Dipali AU - Nehar,Shamshun AU - Paswan,Bhola AU - Rebuffat,Piera AU - Neri,Giuliano AU - Naskar,Ranu AU - Kumari,Kiran AU - Raza,Bushra AU - Rao,N.,Venkat Appa AU - Macchi,Carlo AU - Sen,Nisarga,S. AU - Nussdorfer,Gastone,G. AU - Ahmad,M.,Firoz DA - 2007/07/01 DO - 10.3892/ijmm.20.1.91 EP - 95 IS - 1 JO - Int J Mol Med PY - 2007 SN - 1107-3756 1791-244X SP - 91 ST - IGF-I enhances cortisol secretion from guinea-pig adrenal gland: in vivo and in vitro study T2 - International Journal of Molecular Medicine TI - IGF-I enhances cortisol secretion from guinea-pig adrenal gland: in vivo and in vitro study UR - https://doi.org/10.3892/ijmm.20.1.91 VL - 20 ER -