Dietary protein restriction stress in the domestic fowl (Gallus gallus domesticus) alters adrenocorticotropin-transmembranous signaling and corticosterone negative feedback in adrenal steroidogenic cells

Previous work with growing chickens (Gallus gallus domesticus) indicates th at transient dietary protein restriction induces long-term enhancement of a drenal steroidogenic function in response to adrenocorticotropin (ACTH). Th e present study investigated two possible cellular functions mediating this enhanced response: (a) ACTH signal transduction and dissemination and (b) short-loop feedback inhibition of ACTH-induced corticosterone production by exogenous corticosterone. Cockerels (2 weeks old) were fed isocaloric synt hetic diets containing either 20% (control) or 8% (restriction) soy protein for 4 weeks. Adrenal glands were processed for the isolation of adrenal st eroidogenic cells nearly devoid of chromaffin cells (similar to 90% adrenal steroidogenic cells). Results of experiments to assess signal transduction and dissemination indicated that protein restriction selectively enhanced ACTH-induced corticosterone production mediated by the cyclic AMP (cAMP)-de pendent pathway. In addition, protein restriction substantially counteracte d exogenous corticosterone-dependent inhibition of acute ACTH-induced corti costerone production (by 40.7% vs control). The proximal portion of the cAM P pathway seemed most affected by this stressor. Protein-restricted cells e xhibited enhanced homologous sensitization to ACTH (136% greater than that of control cells) which appeared to be localized at a step(s) prior to or a t the formation to cAMP Also, maximal ACTH-induced cAMP production and sens itivity to ACTH in terms of cAMP production by protein-restricted cells wer e, respectively, 2.2 and 15.8 times those of control cells. However, variab le results were obtained from other experiments designed to pinpoint the al tered early steps in ACTH-transmembranous signaling. For example, with inta ct cells, cAMP responses to cholera toxin (CT) and forskolin (FSK) did not corroborate the results suggesting an augmentation of ACTH-signal transduct ion induced by protein restriction. Furthermore, basal and stimulatable (by ACTH, CT, FSK, and NaF) adenylyl cyclase activities from membranes from pr otein-restricted cells were, respectively, 47.2 and 40.2% less than those f rom control cells (normalized to 10(7) cell equivalents of crude membranes) . Collectively, these findings suggest that protein restriction stress pote ntiates ACTH-induced corticosterone secretion by chicken adrenal steroidoge nic cells in at least two ways: (1) on the proximal end, by modulating unkn own factors which enhance cellular sensitivity to ACTH, ACTH receptor-adeny lyl cyclase coupling, and adenylyl cyclase activity, and (2) on the distal end, by suppressing end-product corticosterone negative feedback, thus faci litating an increase in net corticosterone secretion. (C) 1999 Academic Pre ss.