PTH and PTH-related peptide enhance steroid secretion from human adrenocortical cells.
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 (approximately 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.
Mazzocchi
G
G
Section of Anatomy, Department of Human Anatomy and Physiology, University of Padua, Via Gabelli 65, I-35121 Padua, Italy.
Aragona
F
F
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004963:Estrenes; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C017759:9-(tetrahydro-2-furyl)-adenine; D000450:Aldosterone; C026034:ACTH (7-38); D015544:Inositol 1,4,5-Trisphosphate; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000225:Adenine; D006854:Hydrocortisone