ESTROGEN PRETREATMENT INCREASES ARACHIDONIC-ACID RELEASE BY BRADYKININ-STIMULATED NORMAL HUMAN OSTEOBLAST-LIKE CELLS

Eicosanoids are multifunctional autocrine/paracrine regulators of bone that are enzymatically derived from arachidonic acid (AA). The rate-l imiting step in the eicosanoid biosynthetic pathways may be the releas e of AA from membrane glycerophospholipids by activated phospholipases . Free AA can serve as the substrate for cyclooxygenase(s) or lipoxyge nases that catalyze the commitive steps in eicosanoid synthesis; alter natively, free AA may be used in reacylation processes, resulting in i ts reincorporation into cellular lipids. The hormones 17 beta-estradio l (17 beta-E(2)), dexamethasone (a synthetic glucocorticoid), and 1,25 -dihydroxyvitamin D-3 (1,25(OH)(2)D-3) have been identified as regulat ors of AA metabolism, at various levels, in several tissues including bone. The possibility that these osteotropic steroids modulate the ava ilability of free AA in bone cells was studied in the human osteoblast -like (hOB) cell model system. Following a 48-h steroid pretreatment, bradykinin or the calcium ionophore A23187 were used as agonists to st imulate hOB cell release of AA. The principal findings from these inve stigations were that (1) 17 beta-E(2) pretreatment potentiated the app earance of free AA following bradykinin stimulation of the cells but, did not alter their response to A23187 stimulation; (2) dexamethasone pretreatment limited bradykinin-induced increases in free AA levels bu t did not alter cell response to A23187 stimulation; (3) hOB cells der ived from different trabecular bone compartments (manubrium of the ste rnum, femoral head) differed quantitatively in their responses to brad ykinin stimulation of AA release; and (4) 1,25(OH)(2)D-3 did not effec t AA release stimulated by either agonist. The ability of the steroids to modulate AA release by hOB cells suggests that these hormones may indirectly mediate bone cell responses to other osteotropic hormones t hat act through eicosanoid-dependent processes. (C) 1996 Wiley-Liss, I nc.