Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the actions of 17 beta-estradiol (E2) on the production of cAMP stimulated by synthetic human PTH [hPTH-(1-34)], synthetic hPTH-related protein [hPTHrP-(1-34)], and vasoactive intestinal peptide (VIP) in human (SaOS-2) and rat (ROS 17/2.8) osteoblast-like osteosarcoma cells. In SaOS-2 cells, hPTH-(1-34) (2.5 nM), hPTHrP-(1-34) (2.5 nM), and VIP (10-100 nM) stimulated the accumulation of cAMP markedly (greater than 20- to 30-fold in 1 h). Cells were preincubated in serum-free medium for 4-24 h, then in the absence or presence of E2 for 4 h before a 1-h stimulation with peptide hormone in the absence of E2. In SaOS-2 cells, pretreatment with E2 (10(-12)-10(-8) M) for 4 h inhibited by up to 50% the accumulation of cAMP stimulated by hPTH-(1-34) or hPTHrP-(1-34), but E2 had no inhibitory effect on VIP action. 17 alpha-Estradiol had no inhibitory action on hPTH- or hPTHrP-stimulated accumulation of cAMP at concentrations as high as 10(-8) M. Additional evidence against a nonspecific effect of E2 was the total lack of inhibition of cAMP accumulation stimulated by hPTH-(1-34) or hPTHrP-(1-34) in ROS 17/2.8 cells at concentrations of E2 up to 10(-6) M. We conclude that E2 can act directly and rapidly in human osteoblast-like cells to modulate selectively the ability of hPTH and hPTHrP to enhance the production of cAMP.
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PMID:Direct modulation by estradiol of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein. 290 73

We present evidence that 17 beta-estradiol (17 beta-E2) regulates 1,25(OH)2D3-induced alkaline phosphatase synthesis and osteocalcin secretion by the human osteosarcoma cell line MG-63. When cells were pre-treated with 17 beta-E2 for 48 h prior to treatment with 1,25(OH)2D3 (50 nM) for another 48 h, alkaline phosphatase activity increased by 40% (P < 0.025) with 2 nM 17 beta-E2 and plateaued at levels of 20 and 200 nM 17 beta-E2. Under the same experimental conditions, osteocalcin secretion was enhanced by 37% (P < 0.005) with 2 nM E2. However, 17 beta-E2 had no effect on basal alkaline phosphatase or on osteocalcin secretion. Moreover, simultaneous addition of 17 beta-E2 and 1,25(OH)2D3 to cells did not result in any additional effect over 1,25(OH)2D3 treatment alone. Tamoxifen (10 nM) inhibited 17 beta-E2-induced activities in 1,25(OH)2D3-treated cells while not affecting control cells. Dexamethasone pretreatment (100 nM, 48 h) also stimulated alkaline phosphatase activity in MG-63 cells. Moreover, dexamethasone pretreatment followed by treatment with 17 beta-E2 and 1,25(OH)2D3 gave an additive effect for alkaline phosphatase activity. 17 alpha-Estradiol (17 alpha-E2), a less active form of estrogen, failed to modify, at low concentrations, control or 1,25(OH)2D3-induced alkaline phosphatase synthesis and osteocalcin secretion. In fact, a 100-1000-fold higher concentration of 17 alpha-E2 was necessary to reproduce the effects of 17 beta-E2 on osteocalcin secretion. The addition of insulin-like growth factor I (IGF-I) for 24 h (1-50 ng/ml) to MG-63 cells did not modify 1,25(OH)2D3-induced osteocalcin release from these cells. However, longer incubations with 50 ng/ml IGF-I did reproduce some of the effects observed with 17 beta-E2. Thus, the effects of 17 beta-E2 are probably not related to IGF-I production in MG-63 cells since under these conditions the addition of IGF-I alone should have produced a response at shorter incubation times and in the presence of lower concentrations of IGF-I. Since 17 beta-E2 pretreatment was necessary to observe any effects on 1,25(OH)2D3-induced activities, we hypothesized that 17 beta-E2 regulated 1,25(OH)2D3 receptors in MG-63 cells. When cells were treated with 100 nM 17 beta-E2 for 48 h, the binding affinity was unchanged: 37.3 +/- 1.9 versus 35.1 +/- 0.4 pM for cells whether treated or not with 17 beta-E2, respectively. In contrast, a significant increase in binding capacity (Bmax) was noted (15 +/- 3.5%; P < 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of 17 beta-estradiol on the human osteosarcoma cell line MG-63. 818 30