HORMONAL-REGULATION OF PROSTAGLANDIN PRODUCTION BY RHESUS-MONKEY ENDOMETRIUM

Although there have been numerous studies on the production of prostaglandins (PGs) by human endometrium in vitro during the menstrual cycle, considerable variation exists in the levels reported during the proliferative vs. the secretory phase. Such variation may be due in part to the difficulty in obtaining endometrium from a precisely known hormonal environment and in part to the use of the different culture systems employed. The aim of the present study was to develop a nonhuman primate model in which precisely dated endometrial tissue could be obtained reliably. Moreover, PG levels in the endometrium of the rhesus monkey or other primates have not previously been reported during the artificial menstrual cycle. An important objective in establishing such a model was to permit future manipulations of the cycle in vivo [e.g. by omitting the midcycle estradiol (E) peak] to further dissect specific roles of E and progesterone (P) in regulating PG synthesis during the menstrual cycle. Ovariectomized rhesus monkeys were maintained on a standard artificial menstrual cycle via the insertion and removal of Silastic capsules containing E or P. Samples of endometrium (-50 mg) were obtained by hysterotomy under sterile conditions at predetermined stages of separate menstrual cycles: day 9 (midproliferative; n = 5), day 13 (E peak; n = 3), day 14 (1 day post-E peak; n = 5), and day 23 (midsecretory; n = 8). Measurement of the primary PGs in unextracted medium by RIA over 4 days of organ culture indicated PGF2α > 6-keto-PGF1α > PGE2 > thromboxane-B2, PGD2 > leukotrienes. PGF2α, the most abundant PG produced on the first day of culture, was low on day 9 and increased dramatically on day 13 (P < 0.01). On day 14, PGF2α levels fell significantly only 1 day post-E peak (P < 0.01), while on day 23, after exposure to P in vivo, PGF2α was 10-fold higher (P < 0.01) than on cycle days 9 and 14. The other PGs measured showed a lower but similar profile at the cycle stages examined. Physiological concentrations of P (5.0 ng/mL) added to cycle day 23 cultures in both the absence and presence of low or high E markedly inhibited the high levels of PGs found in day 23 cultures (P < 0.01). These findings 1) confirm that PGF2α is the predominant PG produced by the rhesus monkey endometrium and that the capacity for PGF2α synthesis increases markedly during the secretory phase, 2) indicate that PGF2α output is also stimulated under peak E conditions in vivo and falls significantly only 1 day after the E peak (P < 0.01), and 3) confirm that P added in vitro specifically inhibits the high production of PGs from midsecretory endometrium (P < 0.01), indicating that the withdrawal of P in vivo during luteolysis most likely promotes the increase in PG formation which is associated with the onset of menstruation in primates. © 1990 by The Endocrine Society.