Corticotropin-releasing factor up-regulates its own receptor gene expression in corticotropic adenoma cells in vitro

J Clin Endocrinol Metab. 1997 Apr;82(4):1229-34. doi: 10.1210/jcem.82.4.3883.

Abstract

To investigate the expression of CRF receptor (CRF-R) in human corticotropic adenoma (hCA) cells, we analyzed messenger RNA (mRNA) levels of type-1 CRF-R (CRF-R1). Adenomas were obtained from 10 patients with Cushing's disease. Northern blot analysis using a rat CRF-R1 complementary RNA probe revealed a main hybridization band of 2.7 kilobases in all the hCAs. The CRF-R1 mRNA level significantly increased after 1 h, reached 15-fold the basal level at 8 h, and remained elevated 24 h after the addition of 10 nmol/L CRF in vitro. Dose dependency of the stimulatory effect of CRF was also demonstrated in hCA cells, whereas CRF down-regulated CRF-R1 mRNA levels in rat anterior pituitary (AP) cells. Treatment with dexamethasone or vasopressin decreased the CRF-R1 mRNA level in hCA cells, as observed in rat AP cells. In conclusion, we detected CRF-R1 mRNA in all hCAs tested. The CRF-R1 mRNA level was up-regulated by CRF itself in cultured hCA cells, in contrast to the down-regulation in rat AP cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adrenocorticotropic Hormone / metabolism*
  • Animals
  • Arginine Vasopressin / pharmacology
  • Blotting, Northern
  • Corticotropin-Releasing Hormone / pharmacology*
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects*
  • Glucocorticoids / pharmacology
  • Humans
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / genetics*
  • Recombinant Proteins
  • Tumor Cells, Cultured
  • Up-Regulation*

Substances

  • Glucocorticoids
  • RNA, Messenger
  • Receptors, Corticotropin-Releasing Hormone
  • Recombinant Proteins
  • Arginine Vasopressin
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone