Although there is clinical evidence showing that combined therapy with parathyroid hormone (PTH) and estrogen is additively effective in increasing the bone mass of patients with osteoporosis, the mechanism of the interaction between these hormones remains unclear. The present study was performed to determine whether estrogen would affect osteoblast proliferation and function modulated by PTH in human osteoblastic SaOS-2 cells. Human PTH-(1-34) significantly inhibited [3 H]thymidine (TdR) incorporation, which was attenuated by 24 h pretreatment with 10 10 to 10 7 M 17 -estradiol (17 -E 2 ) in a concentration-dependent manner. PTH significantly stimulated alkaline phosphatase (ALP) activity, collagen synthesis and type-1 procollagen mRNA expression after pretreatment with 17 -E 2 in these cells. Tamoxifen, an anti-estrogen, antagonized these 17 -E 2 -induced effects. Pretreatment with insulin-like growth factor-I (IGF-I) mimicked estrogen action, and coincubation of 3 µg/ml anti-IGF-I antibody antagonized the effects of 17 -E 2 as well as those of IGF-I. In the presence of 17 -E 2 pretreatment, PTH strongly stimulated IGF-binding protein (IGFBP)-5 mRNA expression in these cells, and recombinant IGFBP-5 increased type-1 procollagen mRNA expression and ALP activity. In conclusion, estrogen attenuates PTH-induced inhibition of osteoblast proliferation and PTH stimulates osteoblast function in the presence of estrogen pretreatment. IGF-I and/or IGFBP-5 seemed to be involved in the estrogen-induced modulation of PTH action on osteoblast proliferation and function.
Neuropeptide Y (NPY) and NPY Y2 receptor (Y2R) is involved in the stress-induced visceral obesity in mice. We have previously reported the association between 5'-flanking region of Y2R gene SNPs and plasma HDL-cholesterol levels in healthy subjects. Plasma HDL-cholesterol levels were significantly different in subjects with each SNPs (rs6857530; GG1.5-fold) 743 entities, and down-regulated (<0.67-fold) 492 entities of 54,675 probe sets. BIIE0246-upregulated genes significantly (P-value<0.001) related to gene ontology (GO) categories of 3 biological processes, 7 cellular components and 1 molecular function. Three biological processes were chylomicron remodeling, negative regulation of cholesterol and sterol transport. BIIE0246-downregulated genes significantly related to GO categories of 44 biological processes, 11 cellular components and 1 molecular function. Furthermore, BIIE0246-downregulated genes were significantly involved in 44 pathways (P<0.01), in which sterol responsive element binding protein signaling were included. BIIE0246-upregulated genes were significantly involved in 22 pathways including vitamin B12/ lipoprotein metabolism (P=0.0048). These results suggest that Y2R blockade might inhibit cholesterol synthesis and raise plasma HDL-cholesterol levels, suggesting a new therapeutic drug for dyslipidemia in subjects with specific Y2R SNPs.
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