Effect of phorbol ester on prostaglandin regulation of proliferation in rabbit endometrial cells

Abstract

We have proposed that two of the endogenously synthesized endometrial prostaglandins, prostaglandin F 2α (PGF 2α) and prostaglandin E 1 (PGE 1), play a regulatory role in growth control of the endometrium. PGF 2α increases DNA synthesis and PGE 1 inhibits that effect. Primary cultures of rabbit endometrial cells were used here to examine the effects of the tumor-promoting, diacylglycerol mimicking, phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (TPA), on the prostaglandin control of cell proliferation. TPA treatment of these cultures results in: a decrease in control levels of proliferation and complete inhibition by TPA of PGF 2α stimulated DNA synthesis; a reduction in [ 3H]PGF 2α binding with short term treatment but an increase to above control binding level with long term treatment; an inhibition of the normal PGF 2α stimulated inositol polyphosphate synthesis; and a small increase in accumulation of PGF 2α in the culture media. Furthermore, in this culture system, TPA does not down regulate [ 3H]PGE 1 binding; it does not alter the normal PGE 1 stimulation of cAMP synthesis; and it has no effect on the normal endogenous PGE 1 synthesis by these cultures. The above results are consistent with our previous observations that PGF 2α works through the intracellular messengers inositol polyphosphate/diacylglycerol whereas PGE 1 works through cAMP.