Inhibition of signal transduction by a splice variant of the growth hormone-releasing hormone receptor expressed in human pituitary adenomas.

Abstract

We have previously shown that some of human growth hormone (GH)-producing pituitary adenomas preferentially express a larger transcript of GH-releasing hormone (GHRH) receptor (GHRH-R). This transcriptional variant is presumed to be produced by alternative messenger RNA splicing and contains premature stop codon in frame, predicted to yield a truncated GHRH-R. Functional expression study indicated that the variant receptor was unable to transduct GHRH signals. To determine the functional relationship between the splice-variant and the wild-type GHRH-R, the expression vector for the variant GHRH-R transcript was transfected into COS-7 cells together with or without that for the wild GHRH-R transcript. In cells transfected with both GHRH-R expression vectors, GHRH-dependent cyclic adenosine monophosphate (cAMP) induction was decreased to 39% of that in the cells transfected with the wild-type GHRH-R expression vector alone. This inhibition was found to be irrespective of the concentration (10(-8) to 10(-5) mol/L) of GHRH. These findings suggest that the splice variant form of GHRH-R functions as a dominant-negative modulator in GHRH-induced cellular signaling.

• Authors: T Motomura, K Hashimoto, M Koga, N Arita, T Hayakawa, T Kishimoto, S Kasayama
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 47 Issue 7 Pg. 804-8 (Jul 1998) ISSN: 0026-0495 [Print] United States
• PMID: 9667225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Neuropeptide
• Receptors, Pituitary Hormone-Regulating Hormone
• somatotropin releasing hormone receptor

Topics

• Adenoma (genetics, metabolism)
• Alternative Splicing (physiology)
• Animals
• COS Cells
• Chlorocebus aethiops
• Genetic Vectors (metabolism)
• Humans
• Pituitary Neoplasms (genetics, metabolism)
• Receptors, Neuropeptide (antagonists & inhibitors, genetics, physiology)
• Receptors, Pituitary Hormone-Regulating Hormone (antagonists & inhibitors, genetics, physiology)
• Signal Transduction (genetics)
• Transfection