PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells

Parathyroid hormone (PTH) and PTH-related peptide (PTH-RP) are two hypercal cemic hormones that share a common receptor subtype, the PTH/PTH-RP recepto r. PTH and PTH-RP concentration dependently enhanced basal aldosterone and cortisol secretion from dispersed human adrenocortical cells, with a maxima l effective concentration (similar to2-fold increase) of 10(-8) M. The secr etagogue effect of 10(-8) M PTH or PTH-RP was abolished by the PTH/PTH-RP r eceptor antagonist [Leu(11),D-Trp(12)]-PTH-RP-( 7-34)-amide (10(-6) M). PTH and PTH-RP (10(-8) M) raised cAMP and inositol-triphosphate release by dis persed adrenocortical cells, and these effects were blocked by the adenylat e cyclase inhibitor SQ-22536 (10(-4) M) and the phospholipase C (PLC) inhib itor U-73122 (10(-5) M), respectively. SQ-22536 (10(-4) M) and U-73122 (10( -5) M) partially inhibited aldosterone and cortisol response to 10(-8) M PT H and PTH-RP; when added together, they abolished it. Similar results were obtained by using the protein kinase (PK)A and PKC inhibitors H-89 and calp hostin C (10(-5) M). It is concluded that PTH and PTH-RP exert a sizeable s ecretagogue action on the human adrenal cortex, probably acting through the PTH/PTH-RP receptor coupled with both adenylate cyclase/PKA- and PLC/PKC-d ependent signaling cascades.