Gonadotropin-releasing hormone initiates multiple signaling pathways in human GH-secreting adenomas

Journal of Endocrinological Investigation
Andrea LaniaAnna Spada

Abstract

Abnormal GH responses to GnRH test, observed in about 15% of patients with acromegaly, have been reported exclusively in patients bearing tumors without gsp mutation. The absence of responsiveness to GnRH in gsp+ tumors was not predicted on the basis of the mechanism of GnRH action that mainly involves the activation of calcium and protein kinase C dependent pathways. The aim of the present study was to investigate in detail the transduction of GnRH signaling in these tumors. GH-secreting adenomas removed from patients in vivo responsive to GnRH test were studied. Tumor DNA was screened for Gsalpha and GnRH receptor gene sequences. Intracellular calcium ([Ca2+]i) and cAMP levels were measured in dispersed cells and adenylyl cyclase (AC) activity in membrane preparations. DNA analysis showed wild sequence of both Gsalpha and GnRH receptor genes. GnRH caused a significant increase in intracellular Ca2+ that was associated with a significant stimulation of cAMP accumulation. In these cells neither TRH nor GHRP-6 were effective in causing significant modifications of cAMP levels, despite their ability to increase [Ca2+]i. Finally, GnRH was able to directly stimulate AC from 11.1 +/- 3.3 pmol/mg prot/min to 26.9 +/- 5.4 (p<0.005). W...Continue Reading

References

Jun 1, 1987·Endocrinology·G GiannattasioL Vallar
Oct 21, 1998·Oncogene·N DhanasekaranD Onesime
Dec 24, 1998·Molecular and Cellular Endocrinology·D StanislausP M Conn
Jun 12, 2001·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·H AndoA Urano
Nov 27, 2001·European Journal of Endocrinology·A LaniaA Spada
Jun 27, 2003·Cellular and Molecular Neurobiology·Paul A Insel, Rennolds S Ostrom

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Citations

Jul 13, 2013·European Journal of Endocrinology·Bernhard MayrChristof Schöfl
Mar 21, 2006·Cancer Letters·Sarah KrausRony Seger

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