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

• Published in: American journal of physiology: endocrinology and metabolism 2001-02, Vol.280 (2), p.E209-E213
• Main Authors: Mazzocchi, Giuseppina, Aragona, Francesco, Malendowicz, Ludwik K, Nussdorfer, Gastone G
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adrenal Cortex - cytology; Adrenal Cortex - drug effects; Adrenal Cortex - metabolism; Adrenal Cortex - secretion; Adrenocorticotropic Hormone - pharmacology; Aldosterone - secretion; Cyclic AMP - metabolism; Enzyme Inhibitors - pharmacology; Estrenes - pharmacology; Humans; Hydrocortisone - secretion; Inositol 1,4,5-Trisphosphate - metabolism; Parathyroid Hormone - pharmacology; Parathyroid Hormone-Related Protein; Peptide Fragments - pharmacology; Proteins - pharmacology; Pyrrolidinones - pharmacology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.2001.280.2.e209

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 [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 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