RESUMO
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.
Assuntos
Córtex Suprarrenal/citologia , Córtex Suprarrenal/fisiologia , Hidrocortisona/metabolismo , Fator de Crescimento Insulin-Like I/administração & dosagem , Fator de Crescimento Insulin-Like I/farmacologia , Córtex Suprarrenal/metabolismo , Animais , Captopril/farmacologia , AMP Cíclico/análise , AMP Cíclico/metabolismo , Dexametasona/farmacologia , Cobaias , Hidrocortisona/análise , Hidrocortisona/sangue , Técnicas In Vitro , Fosfatos de Inositol/análise , Fosfatos de Inositol/metabolismo , Masculino , Zona Fasciculada/fisiologia , Zona Reticular/fisiologiaRESUMO
Atrial natriuretic peptide (ANP) is a regulatory hormone widely expressed, along with its receptors, in organs and body tissues. ANP is well known to inhibit aldosterone secretion from mammalian adrenals, but its effect on glucocorticoid-hormone production is controversial. In vivo experiments showed that prolonged ANP administration raised the plasma concentration of cortisol in both normal and dexamethasone/captopril-treated guinea pigs (i.e. in animals with pharmacologically interrupted hypothalamic-pituitary-adrenal axis and renin-angiotensin system). ANP did not affect cortisol secretion from dispersed guinea pig zona fasciculata-reticularis cells, but enhanced catecholamine release from adrenomedullary cells. ANP stimulated cortisol output from guinea pig adrenal slices containing medullary chromaffin tissue, and the beta-adrenoceptor antagonist l-alprenolol blocked this effect. The conclusion is drawn that ANP, when the structural integrity of the adrenal gland is preserved, is able to enhance glucocorticoid secretion in guinea pigs, through an indirect mechanism involving the rise in the catecholamine release, which in turn, acting in a paracrine manner, stimulate secretion of inner adrenocortical cells.
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Fator Natriurético Atrial/farmacologia , Hidrocortisona/metabolismo , Glândulas Suprarrenais/metabolismo , Medula Suprarrenal/efeitos dos fármacos , Medula Suprarrenal/metabolismo , Alprenolol/administração & dosagem , Alprenolol/farmacologia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Fator Natriurético Atrial/administração & dosagem , Captopril/administração & dosagem , Captopril/farmacologia , Catecolaminas/metabolismo , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Epinefrina/metabolismo , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacologia , Cobaias , Hidrocortisona/sangue , Técnicas In Vitro , Injeções Subcutâneas , Masculino , Norepinefrina/metabolismo , Comunicação Parácrina/efeitos dos fármacos , Comunicação Parácrina/fisiologiaRESUMO
Effect of prolonged administration of substance P on the plasma cortisol level in the albino rats has been investigated. An inhibitory impact on intact individuals and a stimulatory effect in pharmacologically annulled rats has been observed. It is concluded that in normal conditions substance P presumably acts as a preventive agent for any excess secretion of cortisol while during stress or disturbed HPA or RAS conditions, it stimulates the secretion of cortisol. An intraglandular modulatory role of substance P has been suggested.