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Regulation of circulating sclerostin levels by sex steroids in women and in men
- Source :
- Journal of Bone and Mineral Research
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Sex steroids are important regulators of bone turnover, but the mechanisms of their effects on bone remain unclear. Sclerostin is an inhibitor of Wnt signaling, and circulating estrogen (E) levels are inversely associated with sclerostin levels in postmenopausal women. To directly test for sex steroid regulation of sclerostin levels, we examined effects of E treatment of postmenopausal women or selective withdrawal of E versus testosterone (T) in elderly men on circulating sclerostin levels. E treatment of postmenopausal women (n = 17) for 4 weeks led to a 27% decrease in serum sclerostin levels [versus +1% in controls (n = 18), p < .001]. Similarly, in 59 elderly men, we eliminated endogenous E and T production and studied them under conditions of physiologic T and E replacement, and then following withdrawal of T or E, we found that E, but not T, prevented increases in sclerostin levels following induction of sex steroid deficiency. In both sexes, changes in sclerostin levels correlated with changes in bone-resorption, but not bone-formation, markers (r = 0.62, p < .001, and r = 0.33, p = .009, for correlations with changes in serum C-terminal telopeptide of type 1 collagen in the women and men, respectively). Our studies thus establish that in humans, circulating sclerostin levels are reduced by E but not by T. Moreover, consistent with recent data indicating important effects of Wnts on osteoclastic cells, our findings suggest that in humans, changes in sclerostin production may contribute to effects of E on bone resorption. © 2011 American Society for Bone and Mineral Research.
- Subjects :
- Adult
Genetic Markers
Male
medicine.medical_specialty
medicine.drug_class
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
Biology
Collagen Type I
Bone resorption
Bone remodeling
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
N-terminal telopeptide
TESTOSTERONE
Internal medicine
BONE TURNOVER
medicine
Humans
Orthopedics and Sports Medicine
SCLEROSTIN
Testosterone
Adaptor Proteins, Signal Transducing
Aged
030304 developmental biology
Aged, 80 and over
Analysis of Variance
0303 health sciences
Estradiol
Osteoprotegerin
Middle Aged
Androgen
ESTROGEN
Endocrinology
chemistry
Sex steroid
Estrogen
Bone Morphogenetic Proteins
Sclerostin
Female
Original Article
Bone Remodeling
Peptides
Biomarkers
Subjects
Details
- ISSN :
- 08840431
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Journal of Bone and Mineral Research
- Accession number :
- edsair.doi.dedup.....45122806b40868d65e8698fd6ad8d49e