TONIC SUPPORT OF LUTEINIZING-HORMONE SECRETION BY ADRENAL PROGESTERONE IN THE OVARIECTOMIZED MONKEY REPLACED WITH MIDFOLLICULAR PHASE LEVELS OF ESTRADIOL

Although it is known that progesterone facilitates the estradiol-induc ed gonadotropin surge at midcycle, its effect on LH secretion at other times of the follicular phase remains to be investigated. In this stu dy, we investigate the role of progesterone on tonic LH secretion in t he ovariectomized primate replaced with estradiol at levels representa tive of the follicular phase. The experiments were performed in nine o variectomized rhesus monkeys, either unreplaced with estradiol or afte r a 5-day estradiol therapy to mimic early follicular (10-36 pg/mL; lo w dose) and midfollicular (medium dose; 40-75 pg/mL) concentrations. W e used two antiprogesterone compounds, RU-486 (5 mg) and ORG-31806 (1 mg), to antagonize endogenous progesterone activity and studied their acute effects on LH secretion in each group. LH concentrations were me asured at 15-min intervals for a 3-h baseline period and during a 5-h period after antagonist administration. LH concentrations remained unc hanged after either antiprogesterone compound or diluent (ethanol) adm inistration in the estrogen-unreplaced monkeys or after low dose estra diol replacement. However, both antiprogesterone compounds significant ly decreased LH secretion in monkeys pretreated with the medium dose o f estradiol; by 5 h, the mean (+/- SE) areas under the LH curve were 5 4.8 +/- 4.1% and 64.0 +/- 4.2% after RU-486 and ORG-31806, respectivel y (P < 0.05 vs. unreplaced and low dose estrogen-replaced groups). To exclude the possibility that the LH response reflects an agonist actio n of the progesterone antagonist, LH responses to progesterone infusio ns (at three doses to reproduce preovulatory, luteal, and pharmacologi cal levels) were also examined in monkeys pretreated with midfollicula r levels of estradiol. In none of these was there a decrease in LK; ra ther, progesterone infusions resulted in an increase in LH secretion i n all three groups (to 115-194% of baseline in seven of eight monkeys) . Finally, we determined that at the dose used in our protocol, neithe r of the two progesterone antagonists was able to prevent dexamethason e-induced cortisol suppression, thus excluding the possibility that re sults after progesterone antagonist administration may reflect a putat ive antiglucocorticoid activity of these compounds. When the doses of the antiprogesterone compounds were increased 6 times, only RU-486 cou nteracted the effect of dexamethasone on cortisol. In summary, our dat a indicate support by progesterone of tonic LH secretion in the nonhum an primate under estrogenic conditions similar to the midfollicular ph ase of the menstrual cycle. Significantly, because the experiments wer e performed in ovariectomized monkeys, and endogenous progesterone was most probably of adrenal origin, the data also demonstrate a role of the hypothalamo-pituitary-adrenal axis in support of gonadotropin secr etion.