Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schwetz, V.
The Endocrine Role of the Skeleton - Osteocalcin, Glucose Metabolism and Fertility
[ Dissertation ] Medical University of Graz; 2013. pp. 119
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- Autor*innen der Med Uni Graz:
- Theiler-Schwetz Verena
- Betreuer*innen:
- Leithner Andreas
- Obermayer-Pietsch Barbara
- Pieber Thomas
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- Abstract:
- Osteocalcin (OC), released by osteoblasts and known as a marker of bone turnover, influences both energy metabolism as well as male fertility in murine models. Results from clinical studies are controversial. Single nucleotide polymorphisms in the OC gene have been investigated and a haplotype of three SNPs associated with body mass index (BMI). In the first part, we investigated the effect of a 75g oral glucose tolerance test (OGTT) on total OC, undercarboxylated (ucOC) and carboxylated OC (cOC) in insulin-resistant (IR) and non-insulin-resistant (nIR) premenopausal women. Further, the relationship of changes in OC, ucOC, and cOC with AUCinsulin and Matsuda index were examined. In this cross-sectional study, OGTT were performed in 105 premenopausal women, 18 of which were insulin-resistant (HOMA-IR > 2.6) and 87 of which were not. Changes in total OC, ucOC, and cOC were evaluated 60 and 120 minutes after glucose load. At baseline, total OC, cOC, and ucOC were significantly lower in insulin-resistant women. In non-insulin-resistant women, total OC, ucOC and cOC decreased significantly while in insulin-resistant women, none of the parameters of OC did. In stepwise linear regression analyses adjusted for age and BMI, the declines in OC and cOC significantly predicted AUCinsulin and Matsuda. Glucose intake in non-insulin-resistant women is accompanied by decreases in the levels of OC, ucOC, and cOC, the extent of which predicts insulin resistance and sensitivity in premenopausal women. In insulin-resistant women these parameters appeared suppressed. Osteoblast responses to oral glucose in insulin-resistant and non-insulin-resistant women might differ ¿ OC reflects this finding. The aim of the second part was to assess the association of OC, ucOC, cOC with testosterone and sperm count in 159 men from infertile couples. For this purpose, testosterone, LH, OC, ucOC were measured and semen analysis performed. cOC and OC correlated weakly but significantly with testosterone, but not after adjustment for BMI and age. No significant correlations were observed between parameters of OC and sperm count, semen volume and number of vital sperms. In binary logistic regression analyses, none of the parameters of OC were predictors of oligozoospermia after adjustment for age and BMI or WHR. The current data show that OC is only modestly associated with male fertility in young men from infertile couples. The third aim was to test the association of three OC polymorphisms with BMI and with parameters of glucose and lipid metabolism in women with polycystic ovary syndrome (PCOS). Metabolic and anthropometric measurements and oral glucose tolerance tests were performed in 680 PCOS women and genotyping of three OC SNPs (rs2758605, rs1543294, rs2241106) was carried out. As for rs2241106, 340 women were carriers of the CC genotype, 278 of the CG genotype, and 62 of the GG genotype. CC genotype carriers had a significantly higher BMI compared to CG genotype carriers, but not compared to women carrying the GG genotype. No difference between the groups could be identified concerning the parameters of glucose and lipid metabolism analyzed. As for rs1543294 and rs2758605, there was no difference between the genotypes concerning the parameters investigated. These data confirm the association of the SNP rs2241106 with BMI in a cohort of women with PCOS. The three OC SNPs did not show an association with parameters of glucose and lipid metabolism in this cohort. To conclude, bone and glucose metabolism seem to be related via OC. In humans, a stronger role of the carboxylated fraction of OC is suggested. OC polymorphisms are associated with BMI in healthy individuals and women with polycystic ovary syndrome, while data on other patient cohorts are still lacking. The association of OC with testosterone is weak. OC and parameters of semen analysis do not seem to be associated so far ¿ however, more data are needed to support these findings.