Differential control of corticotroph Ca2+ signalling by corticotrophin-releasing hormone and arginine vasopressin

Corticotroph cells convert hypothalamic inputs into adrenocorticotrophic hormone secretion via intracellular calcium (Ca2+) signalling, but how they integrate corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) across physiological concentration ranges remains unclear. Here, we quantified intracellular Ca2+ responses in isolated rat corticotrophs to CRH and AVP, applied alone and in combination, to characterise response magnitude, temporal dynamics, and cell recruitment. Both secretagogues increased Ca2+ signalling in a concentration-dependent manner, but with distinct effects: AVP generally evoked larger responses, faster response onset, and greater cell recruitment than CRH when applied alone. Under co-stimulation, increasing CRH concentration increased the proportion of cells classified as synergistic without altering positive synergy values, suggesting CRH-dependent control of interaction likelihood rather than interaction strength. Marked cell-to-cell heterogeneity was observed across all conditions, consistent with corticotroph subpopulations differing in activation thresholds. Together, these findings show that AVP drives broad corticotroph recruitment, whereas CRH modulates how corticotrophs integrate convergent inputs, defining complementary roles in shaping pituitary output.