Expression of estrogen receptor α and β in the rhesus monkey corpus luteum during the menstrual cycle:: Regulation by luteinizing hormone and progesterone

There are conflicting reports on the presence or absence of estrogen receptor (ER) in the primate corpus luteum, and the discovery of a second type of estrogen receptor, ER beta, adds an additional level of complexity. To reevaluate ER expression in the primate luteal tissue, we used semiquantitative RT-PCR based assays and Western blotting to assess ER alpha and beta messenger RNA (mRNA) and protein levels in corpora lutea (n = 3/stage) obtained from adult female rhesus monkeys at early (days 3-5), mid (days 6-8), mid-late (days 10-12), and late (days 14-16) luteal phase of the natural menstrual cycle. ER alpha mRNA levels did not vary across the stages of the luteal phase, and ER alpha protein was not consistently detected in luteal tissues. However, ER beta mRNA and protein levels were detectable in early and mid luteal phases and increased (P < 0.05) to peak levels at mid-late luteal phase before declining by late luteal phase. To determine if ER beta mRNA expression in the corpus luteum is regulated by LH, monkeys received the GnRH antagonist antide either alone or with 3 daily injections of LH to simulate pulsatile LH release. Treatment with antide alone or concomitant LH administration did not alter luteal ERP mRNA levels. When monkeys also received the 3 beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERP mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERP mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ER beta expression in the primate corpus luteum during the menstrual cycle, consistent with a role for estrogen in the regulation of primate luteal function and life span via a receptor (ER beta)-mediated pathway. Increased ER beta expression in the progestin-depleted corpus luteum during LH exposure suggests that the relative progestin deprivation experienced by the corpus luteum between LH pulses may enhance luteal sensitivity to estrogens during the late luteal phase of the menstrual cycle.