Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.
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 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/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 microg 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.
Mantovani
Giovanna
G
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20122 Milan, Italy.
Maghnie
Mohamad
M
Weber
Giovanna
G
De Menis
Ernesto
E
Brunelli
Valeria
V
Cappa
Marco
M
Loli
Paola
P
Beck-Peccoz
Paolo
P
Spada
Anna
A
D000324:Adrenocorticotropic Hormone / Q000502:physiology; D000328:Adult; D002648:Child; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology*; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011547:Pseudohypoparathyroidism / Q000097:blood / Q000235:genetics*
D006728:Hormones; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D013007:Growth Hormone-Releasing Hormone; D019205:GTP-Binding Protein alpha Subunits, Gs