Expression of estrogen receptor alpha and beta 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, ERbeta, 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 ERalpha 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. ERalpha mRNA levels did not vary across the stages of the luteal phase, and ERalpha protein was not consistently detected in luteal tissues. However, ERbeta 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 ERbeta 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 ERbeta mRNA levels. When monkeys also received the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane to reduce luteal progesterone production, luteal ERbeta mRNA levels were 3-fold higher (P < 0.05) than in monkeys receiving antide + LH only. Replacement of progestin activity with R5020 reduced luteal ERbeta mRNA levels to those seen in animals receiving antide + LH. Thus, there is dynamic ERbeta 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 (ERbeta)-mediated pathway. Increased ERbeta 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.
Duffy
D M
DM
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA. duffyd@ohsu.edu
Chaffin
C L
CL
Stouffer
R L
RL
D000818:Animals; D003338:Corpus Luteum / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D007986:Luteinizing Hormone / Q000502:physiology*; D008253:Macaca mulatta; D008597:Menstrual Cycle; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000097:blood / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone