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Am J Physiol Endocrinol Metab 280: E209-E213, 2001;
0193-1849/01 $5.00
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Vol. 280, Issue 2, E209-E213, February 2001

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

Giuseppina Mazzocchi1, Francesco Aragona2, Ludwik K. Malendowicz1, and Gastone G. Nussdorfer1

1 Section of Anatomy, Department of Human Anatomy and Physiology and 2 Department of Urology, University of Padua, I-35121 Padua, Italy

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.

aldosterone; cortisol; protein kinases A and C


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