Direct modulation by estradiol of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein.
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.
Fukayama
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S
Laboratory of Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.
Tashjian
A H
AH
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins; D051381:Rats; D019379:Teriparatide; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); D014660:Vasoactive Intestinal Peptide; D004958:Estradiol