help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goad, D. L.
Right arrow Articles by Tashjian, A. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goad, D. L.
Right arrow Articles by Tashjian, A. H., Jr

Endocrinology, Vol 133, 1585-1592, Copyright © 1993 by Endocrine Society

ARTICLES

Insulin-like growth factor-I inhibits parathyroid hormone-stimulated and enhances prostaglandin E2-stimulated adenosine 3',5'-monophosphate production by human osteoblast-like SaOS-2 cells

DL Goad and AH Tashjian Jr
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.

Insulin-like growth factor-1 (IGF-I), an endocrine and autocrine/paracrine factor that enhances collagen synthesis and bone matrix formation by osteoblasts, has been implicated in the coupling of bone formation with bone resorption. We have found, using SaOS-2 osteoblastic cells, that IGF-I inhibits PTH-stimulated cAMP production. Pretreatment of SaOS-2 cells with IGF-I for 24 h inhibited cAMP production stimulated by PTH with an IC50 of 1 nM and maximal inhibition to 10-20% of control values at an IGF-I concentration of 10 nM. Pretreatment with IGF-I had no effect on vasoactive intestinal peptide-stimulated cAMP production, but it enhanced cAMP production stimulated by prostaglandin E2 (PGE2) by as much as 5-fold at a concentration of 10 nM and with an EC50 of 1 nM. Pretreatment of SaOS-2 cells with IGF-I did not affect cholera toxin- or forskolin-stimulated cAMP accumulation. Taken together, these findings indicated that IGF-I did not affect Gs alpha, coupling of Gs alpha to adenylate cyclase, or adenylate cyclase itself. Binding experiments using [125I] chicken PTH- related peptide (PTHrP)-(1-36)-[Tyr36]NH2 demonstrated that IGF-I reduced PTH/PTHrP receptor number to 25% of the control value without affecting receptor affinity. IGF-I and the related growth factors, insulin and IGF-II, inhibited PTH-stimulated cAMP production with a rank order of potency of IGF-I > or = IGF-II > insulin, indicating that the actions of IGF-I on SaOS-2 cells were probably mediated by the IGF- I receptor. We conclude that physiologically relevant concentrations of IGF-I specifically inhibited PTH-stimulated and enhanced PGE2- stimulated production of cAMP by an action at the level of PTH and PGE2 receptors and/or coupling of the receptors to Gs alpha.


This article has been cited by other articles:


Home page
 EndocrinologyHome page
A. Quesada and A. M. Etgen
Insulin-Like Growth Factor-1 Regulation of {{alpha}}1-Adrenergic Receptor Signaling Is Estradiol Dependent in the Preoptic Area and Hypothalamus of Female Rats
Endocrinology, February 1, 2001; 142(2): 599 - 607.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Kawane and N. Horiuchi
Insulin-Like Growth Factor I Suppresses Parathyroid Hormone (PTH)/PTH-Related Protein Receptor Expression via a Mitogen-Activated Protein Kinase Pathway in UMR-106 Osteoblast-Like Cells
Endocrinology, February 1, 1999; 140(2): 871 - 879.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1993 by The Endocrine Society