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Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with growth hormone deficiency in response to growth hormone treatment.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2015 Feb; Vol. 100 (2), pp. 736-43. Date of Electronic Publication: 2014 Dec 02. - Publication Year :
- 2015
-
Abstract
- Context: Growth hormone (GH) substitution of adult-onset growth hormone deficiency (aoGHD) patients partially reverses unfavorable body composition profile. Wnt signaling pathway has being acknowledged as an important modulator of bone mass and of energy metabolism in adipose tissue and in β-cells.<br />Objective: To assess the role of selected Wnt antagonists in bone and glucose metabolism before and after GH replacement in aoGHD.<br />Patients and Methods: Patients from two randomized placebo-controlled studies of GH replacement in aoGHD were used. In study 1, 39 patients received GH or placebo for 9 months with 4 months wash-out. In study 2, iliac bone biopsies were obtained before and after GH or placebo (n = 10 each) for 12 months. Body composition and serum (study 1) and bone matrix (study 2) levels of Wnt antagonists (DKK-1, sFRP-3, WIF-1, and SOST) were quantified before and after GH. In vitro effect of GH and IGF-1 on DKK-1 secretion and expression of Wnt signaling modulators was assessed in human osteoblasts and mature adipocytes.<br />Results: GH replacement increased circulating and bone matrix levels of DKK-1, but not sFRP-3, WIF-1, and SOST. Furthermore, DKK-1 secretion increased in human osteoblasts stimulated by GH in vitro, with no effects on other cells. At baseline and after treatment, circulating DKK-1 was negatively associated with bone mass, but not fat mass or measures of insulin resistance, in aoGHD patients.<br />Conclusions: An increase in DKK-1 may limit the effects of GH on bone mass, but does not seem to impact the increase in insulin resistance following GH substitution.
- Subjects :
- Adaptor Proteins, Signal Transducing blood
Adaptor Proteins, Signal Transducing metabolism
Adipocytes drug effects
Adipocytes metabolism
Adult
Bone Matrix drug effects
Bone Morphogenetic Proteins blood
Bone Morphogenetic Proteins metabolism
Dwarfism, Pituitary blood
Dwarfism, Pituitary drug therapy
Female
Genetic Markers
Human Growth Hormone pharmacology
Humans
Ilium drug effects
Ilium metabolism
Insulin-Like Growth Factor I pharmacology
Intercellular Signaling Peptides and Proteins blood
Male
Middle Aged
Muscle Proteins blood
Muscle Proteins metabolism
Osteoblasts drug effects
Osteoblasts metabolism
Repressor Proteins blood
Repressor Proteins metabolism
Bone Matrix metabolism
Dwarfism, Pituitary metabolism
Human Growth Hormone therapeutic use
Intercellular Signaling Peptides and Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 100
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 25459913
- Full Text :
- https://doi.org/10.1210/jc.2014-2912