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

Abstract

Parathyroid hormone (PTH) and PTH-related peptide (PTH-RP) are two hypercalcemic hormones that share a common receptor subtype, the PTH/PTH-RP receptor. PTH and PTH-RP concentration dependently enhanced basal aldosterone and cortisol secretion from dispersed human adrenocortical cells, with a maximal effective concentration (∼2-fold increase) of 10−8 M. The secretagogue effect of 10−8 M PTH or PTH-RP was abolished by the PTH/PTH-RP receptor antagonist [Leu11,d-Trp12]-PTH-RP-(7–34)-amide (10−6 M). PTH and PTH-RP (10−8 M) raised cAMP and inositol-triphosphate release by dispersed adrenocortical cells, and these effects were blocked by the adenylate cyclase inhibitor SQ-22536 (10−4 M) and the phospholipase C (PLC) inhibitor 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 PTH 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 calphostin C (10−5 M). It is concluded that PTH and PTH-RP exert a sizeable secretagogue action on the human adrenal cortex, probably acting through the PTH/PTH-RP receptor coupled with both adenylate cyclase/PKA- and PLC/PKC-dependent signaling cascades.