Stimulation of cortisol release by the N terminus of teleost parathyroid hormone-related protein in interrenal cells in vitro

Endocrinology. 2005 Jan;146(1):71-6. doi: 10.1210/en.2004-0644. Epub 2004 Sep 30.

Abstract

The mode of action of PTHrP in the regulation of sea bream (Sparus auratus) interrenal cortisol production was studied in vitro using a dynamic superfusion system. Piscine (1-34)PTHrP (10(-6)-10(-11) M) stimulated cortisol production in a dose-dependent manner. The ED50 of (1-34)PTHrP was 2.8 times higher than that of (1-39)ACTH, and maximum increase in cortisol production in response to 10(-8) M of (1-34)PTHrP was approximately 7-fold lower than for 10(-8) M of (1-39)ACTH. In contrast to (1-34)PTHrP, piscine (10-20)PTHrP, (79-93)PTHrP, and (100-125)PTHrP (10(-9)-10(-7) M) did not stimulate cortisol production. The effect of piscine (1-34)PTHrP on cortisol production was abolished by N-terminal peptides in which the first amino acid (Ser) was absent and by simultaneous addition of inhibitors of the adenylyl cyclase-protein kinase A and phospholipase C-protein kinase C intracellular pathways but not by each separately. The PTHrP-induced signal transduction was further investigated by measurements of cAMP production and [H3]myo-inositol incorporation in an interrenal cell suspension. Piscine (1-34)PTHrP increased cAMP and total inositol phosphate accumulation, which is indicative that the mechanism of action of PTHrP in interrenal tissue involves the activation of both the adenylyl cyclase-cAMP and phospholipase C-inositol phosphate signaling pathways. These results, together with the expression of mRNA for PTHrP and for PTH receptor (PTHR) type 1 and PTHR type 3 receptors in sea bream interrenal tissue, suggest a specific paracrine or autocrine steroidogenic action of PTHrP mediated by the PTHRs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Adrenocorticotropic Hormone / pharmacology
  • Amino Acid Sequence
  • Animals
  • Cyclic AMP / metabolism
  • Hydrocortisone / metabolism*
  • Inositol / metabolism
  • Kidney / cytology
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Parathyroid Hormone-Related Protein / chemistry*
  • Parathyroid Hormone-Related Protein / genetics
  • Parathyroid Hormone-Related Protein / pharmacology*
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Sea Bream / metabolism*
  • Signal Transduction / physiology
  • Type C Phospholipases / metabolism

Substances

  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • parathyroid hormone-related protein (1-34)
  • Inositol
  • Adrenocorticotropic Hormone
  • Cyclic AMP
  • Type C Phospholipases
  • Adenylyl Cyclases
  • Hydrocortisone