HORMONAL-REGULATION OF ENDOMETRIAL PROSTAGLANDIN-F(2-ALPHA) PRODUCTION DURING THE LUTEAL-PHASE OF THE RHESUS-MONKEY

To study the hormonal regulation of prostaglandin (PG) production by the endometrium during the luteal phase of the primate menstrual cycle, the standard artificial menstrual cycle (SAMC) of the rhesus monkey was manipulated (MAMC) such that in one group of monkeys, there was an absence of the mid-cycle peak of estradiol-17beta (E), but normal luteal phase progesterone (P). In the second group, there was a mid-cycle peak of E, but no luteal phase P. The accumulation of PGF2alpha in tissue culture medium from explants of endometrium obtained on cycle Day 14 or 23 of the MAMC was compared to the accumulation of PGF2alpha from explants on cycle Day 14 or 23 of the SAMC (expressed as mean ng +/- SEM/mg/24 h). Omission of the mid-cycle E peak in the MAMC did not alter endometrial PGF2alpha production in vitro on cycle Day 14, compared to the SAMC; whereas, on cycle Day 23 PGF2alpha, production was reduced (35.1 +/- 6.4 ng/mg/24 h), compared to that in the SAMC (53.8 +/- 10.3 ng/mg/24 h; p = 0.06). Omission of P during the MAMC resulted in higher PGF2alpha production in vitro on cycle Day 14 (p < 0.01) and lower PGF2alpha production on cycle Day 23 (p = 0.05), compared to that in the SAMC on these days. When P (5.0 ng/ml) was added in vitro to Day 23 endometrium, after omission of the mid-cycle E peak, PGF2alpha production was inhibited by 45 +/- 8%, compared to an inhibition of 80 +/- 4% in the SAMC on Day 23 (p < 0.01). When P (5.0 ng/ml) was added in vitro to Day 23 endometrium, after the omission of P during the luteal phase, the inhibition of PGF2alpha production was more intense at 95 +/- 1%, compared to 80 +/- 4% on Day 23 of the SAMC (p < 0.05). We conclude the following: 1) in the presence of the mid-cycle peak of E, the enhancement in P priming in vivo, as shown by the increase in endometrial PGF2alpha production in vitro, and the enhancement of P inhibition of PGF2alpha production by P added in vitro, may be mediated by an increase in P receptors induced by the mid-cycle peak of E. 2) Removal of P during the luteal phase of the cycle reduces the biosynthetic capacity of the endometrium for PGF2alpha production, thus confirming the in vivo priming effect of P in this species. 3) On the basis of the present results obtained by omission of the mid-cycle peak of E, or omission of luteal phase P, the marked reduction in PGF2alpha synthesis that we previously observed on cycle Day 14 of the SAMC (i.e., only one day after the mid-cycle peak of E) may now be explained by the rapid rise in plasma levels of P and the abrupt decline in plasma levels of E that occur on cycle Day 14.