title: IGF-I enhances cortisol secretion from guinea-pig adrenal gland: in vivo and in vitro study.
abstract: 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.
authors.affiliation: Department of Zoology, Ranchi University, Ranchi, India.
authors.forename: Dipali
authors.initials: D
authors.lastname: Raha
authors.forename: Shamshun
authors.initials: S
authors.lastname: Nehar
authors.forename: Bhola
authors.initials: B
authors.lastname: Paswan
authors.forename: Piera
authors.initials: P
authors.lastname: Rebuffat
authors.forename: Giuliano
authors.initials: G
authors.lastname: Neri
authors.forename: Ranu
authors.initials: R
authors.lastname: Naskar
authors.forename: Kiran
authors.initials: K
authors.lastname: Kumari
authors.forename: Bushra
authors.initials: B
authors.lastname: Raza
authors.forename: N Venkat Appa
authors.initials: NV
authors.lastname: Rao
authors.forename: Carlo
authors.initials: C
authors.lastname: Macchi
authors.forename: Nisarga S
authors.initials: NS
authors.lastname: Sen
authors.forename: Gastone G
authors.initials: GG
authors.lastname: Nussdorfer
authors.forename: M Firoz
authors.initials: MF
authors.lastname: Ahmad
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000032:analysis / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D015383:Zona Fasciculata / Q000502:physiology; D015385:Zona Reticularis / Q000502:physiology
chemical_list: D007295:Inositol Phosphates; C092449:inositol 1,2,3-trisphosphate; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D002216:Captopril; D000242:Cyclic AMP; D006854:Hydrocortisone