Direct Modulation by Estradiol of the Response of Human Bone Cells (SaOS-2) to Human Parathyroid Hormone (PTH) and PTH-Related Protein*

Abstract

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 (>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.