Eldering J A, Nay M G, Hoberg L M, Longcope C, McCracken J A
Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545.
J Clin Endocrinol Metab. 1990 Sep;71(3):596-604. doi: 10.1210/jcem-71-3-596.
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 non-human 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 (approximately 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 PGF2 alpha greater than 6-keto-PGF1 alpha greater than PGE2 greater than thromboxane-B2, PGD2 greater than leukotrienes. PGF2 alpha, the most abundant PG produced on the first day of culture, was low on day 9 and increased dramatically on day 13 (P less than 0.01). On day 14, PGF2 alpha levels fell significantly only 1 day post-E peak (P less than 0.01), while on day 23, after exposure to P in vivo, PGF2 alpha was 10-fold higher (P less than 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 less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
尽管在月经周期中已经有大量关于人子宫内膜体外产生前列腺素（PGs）的研究，但在增殖期与分泌期所报道的水平存在相当大的差异。这种差异部分可能是由于难以从精确已知的激素环境中获取子宫内膜，部分是由于所采用的不同培养系统。本研究的目的是建立一种非人类灵长类动物模型，在该模型中可以可靠地获取精确分期的子宫内膜组织。此外，此前尚未报道过恒河猴或其他灵长类动物在人工月经周期中子宫内膜的PG水平。建立这样一个模型的一个重要目标是允许未来在体内对周期进行操作[例如通过省略周期中期的雌二醇（E）峰值]，以进一步剖析E和孕酮（P）在月经周期中调节PG合成的具体作用。通过插入和取出含有E或P的硅橡胶胶囊，对去卵巢的恒河猴维持标准的人工月经周期。在单独月经周期的预定阶段，通过无菌条件下的子宫切开术获取子宫内膜样本（约50毫克）：第9天（增殖中期；n = 5）、第13天（E峰值；n = 3）、第14天（E峰值后1天；n = 5）和第23天（分泌中期；n = 8）。通过放射免疫分析法在器官培养的4天内对未提取培养基中的主要PGs进行测量，结果表明前列腺素F2α（PGF2α）> 6 - 酮 - 前列腺素F1α（6 - keto - PGF1α）> 前列腺素E2（PGE2）> 血栓素B2（thromboxane - B2），前列腺素D2（PGD2）> 白三烯。PGF2α是培养第一天产生的最丰富的PG，在第9天较低，在第13天显著增加（P < 0.01）。在第14天，PGF2α水平仅在E峰值后1天显著下降（P < 0.01），而在第23天，在体内暴露于P后，PGF2α比第9天和第14天高10倍（P < 0.01）。在所检测的周期阶段，其他测量的PGs显示出较低但相似的变化趋势。在第23天的培养物中，无论有无低或高剂量的E，添加生理浓度的P（5.0 ng/mL）均显著抑制了第23天培养物中发现的高水平PGs（P < 0.01）。（摘要截断于400字）
