help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Mantovani, G.
Right arrow Articles by Spada, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mantovani, G.
Right arrow Articles by Spada, A.
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 9 4070-4074
Copyright © 2003 by The Endocrine Society

Special Feature

Growth Hormone-Releasing Hormone Resistance in Pseudohypoparathyroidism Type Ia: New Evidence for Imprinting of the Gs{alpha} Gene

Giovanna Mantovani, Mohamad Maghnie, Giovanna Weber, Ernesto De Menis, Valeria Brunelli, Marco Cappa, Paola Loli, Paolo Beck-Peccoz and Anna Spada

Institute of Endocrine Sciences (G.M., P.B.-P., A.S.), University of Milan, Ospedale Maggiore Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20122 Milan, Italy; Department of Pediatrics (M.M.), Policlinico S. Matteo IRCCS, University of Pavia, 27100 Pavia, Italy; Pediatric Department, Endocrine Unit (G.W.), Ospedale S. Raffaele, University of Milan, 20100 Milan, Italy; I Divisione Medica (E.D.M.), Ospedale Generale, 31100 Treviso, Italy; Department of Pediatric Endocrinology (V.B.), Ospedale Buzzi, 20100 Milan, Italy; Bambino Gesù (M.C.), Children’s Hospital, Palidoro, 00010 Rome, Italy; and Department of Endocrinology (P.L.), Niguarda Ospedale Ca’ Granda, 20100 Milan, Italy

Address all correspondence and requests for reprints to: Professor Anna Spada, Istituto di Scienze Endocrine-Pad. Granelli, Ospedale Maggiore Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via Francesco Sforza, 35, 20122 Milano, Italy. E-mail: anna.spada{at}unimi.it.

Heterozygous inactivating mutations in the Gs{alpha} gene cause Albright’s hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs{alpha} transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs{alpha}-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6–8.6 µg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 µg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 µg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs{alpha} imprinting in human pituitary.

This work was partially supported by Ministero dell’Università e della Ricerca Scientifica e Tecnologica Grant 2001068427 and Ricerca Corrente Funds of Ospedale Maggiore IRCCS, Milan.

Abbreviations: AHO, Albright’s hereditary osteodystrophy; BMI, body mass index; IGFBP, IGF-binding protein; PHP, pseudohypoparathyroidism; PHP Ia, PHP type Ia.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
A. Plagge, G. Kelsey, and E. L Germain-Lee
Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse
J. Endocrinol., February 1, 2008; 196(2): 193 - 214.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Mantovani, S. Bondioni, A. Linglart, M. Maghnie, M. Cisternino, S. Corbetta, A. G. Lania, P. Beck-Peccoz, and A. Spada
Genetic Analysis and Evaluation of Resistance to Thyrotropin and Growth Hormone-Releasing Hormone in Pseudohypoparathyroidism Type Ib
J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3738 - 3742.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. N. Long, S. McGuire, M. A. Levine, L. S. Weinstein, and E. L. Germain-Lee
Body Mass Index Differences in Pseudohypoparathyroidism Type 1a Versus Pseudopseudohypoparathyroidism May Implicate Paternal Imprinting of G{alpha}s in the Development of Human Obesity
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1073 - 1079.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. E. Molitch, D. R. Clemmons, S. Malozowski, G. R. Merriam, S. M. Shalet, M. L. Vance, and for The Endocrine Society's Clinical Guidelines Su
Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline
J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1621 - 1634.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Linglart, M. J. Mahon, M. A. Kerachian, D. M. Berlach, G. N. Hendy, H. Juppner, and M. Bastepe
Coding GNAS Mutations Leading to Hormone Resistance Impair in Vitro Agonist- and Cholera Toxin-Induced Adenosine Cyclic 3',5'-Monophosphate Formation Mediated by Human XL{alpha}s
Endocrinology, May 1, 2006; 147(5): 2253 - 2262.
[Abstract] [Full Text] [PDF]

Home page
 IBMS BoneKEyHome page
M. Bastepe and H. Juppner
Pseudohypoparathyroidism, Gs{alpha}, and the GNAS Locus
IBMS BoneKEy, December 1, 2005; 2(12): 20 - 32.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
E. L. Germain-Lee, W. Schwindinger, J. L. Crane, R. Zewdu, L. S. Zweifel, G. Wand, D. L. Huso, M. Saji, M. D. Ringel, and M. A. Levine
A Mouse Model of Albright Hereditary Osteodystrophy Generated by Targeted Disruption of Exon 1 of the Gnas Gene
Endocrinology, November 1, 2005; 146(11): 4697 - 4709.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
N. Wettschureck and S. Offermanns
Mammalian G Proteins and Their Cell Type Specific Functions
Physiol Rev, October 1, 2005; 85(4): 1159 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Mantovani, S. Bondioni, M. Locatelli, C. Pedroni, A. G. Lania, E. Ferrante, M. Filopanti, P. Beck-Peccoz, and A. Spada
Biallelic Expression of the Gs{alpha} Gene in Human Bone and Adipose Tissue
J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6316 - 6319.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. S. Weinstein, J. Liu, A. Sakamoto, T. Xie, and M. Chen
Minireview: GNAS: Normal and Abnormal Functions
Endocrinology, December 1, 2004; 145(12): 5459 - 5464.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Bastepe and H. Juppner
Pseudohypoparathyroidism and Mechanisms of Resistance toward Multiple Hormones: Molecular Evidence to Clinical Presentation
J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4055 - 4058.
[Full Text] [PDF]


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 © 2003 by The Endocrine Society