Effects of Different Gonadotropin Pulse Frequencies on Corpus Luteum Function during the Menstrual Cycle of Rhesus Monkeys*

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Abstract
In the nonfertile menstrual cycle, the frequency of episodic LH secretion declines from approximately 1 pulse/h in the early luteal phase to 1 pulse/4-8 h in the mid- to late luteal phase, but the relevance of this phenomenon to the initiation of functional luteal regression is not completely understood. We investigated whether a reduction in LH pulse frequency causes a decline in luteal progesterone production by experimentally reducing LH pulse frequency during the early luteal phase, and measured the effects on the subsequent plasma progesterone pattern and the onset of luteal regression. Rhesus monkeys were rendered anovulatory by placing radiofrequency lesions in the arcuate region of the medial basal hypothalamus or surgically transecting the hypothalamic-pituitary stalk. Endogenous gonadotropin secretion and ovulatory menstrual cycles were restored by pulsatile infusion of synthetic GnRH at a frequency of 1 pulse/h. Commencing on days 3-6 of the luteal phase, GnRH frequency was changed to either 1 pulse/8 h (four animals) or 1 pulse/24 h (four animals) or maintained at the standard 1 pulse/h frequency (four animals). Luteal phase of 13- to 17-day duration were observed in all animals kept on the 1 pulse/h frequency and in three of four animals in which the frequency was changed to 1 pulse/8 h on day 3 of the luteal phase. Daily midluteal phase (days 5-10) plasma progesterone levels observed in response to the 1 pulse/h and 1 pulse/8 h infusion regimens were similar (mean .+-. SE, 4.1 .+-. 0.4 vs. 3.2 .+-. 0.4 ng/ml; P > 0.1). In contrast, short luteal phases were observed in all animals after the LH pulse frequency was reduced to 1 pulse/24 h. Comparison of plasma LH responses to a representative GnRH pulse of each GnRH infusion regimen revealed that the maximal LH levels attained in response to 1 pulse/8 h (47.5 .+-. 11.5 ng/ml) were significantly greater (P < 0.05) than the maximal LH levels attained in response to 1 pulse/h (30.5 .+-. 3.2 ng/ml) or 1 pulse/24 h (27.2 .+-. 5.0 ng/ml). Progesterone levels remained elevated for 140-200 min after the LH pulse resulting from the 1 pulse/8 h infusion regimen. In response to the 1 pulse/24 h infusion regimen, plasma progesterone levels remained elevated for 60 min after the LH pulse. These results demonstrated that a GnRH, hence LH pulse frequency of 1 pulse/8 h is able to maintain luteal function and thus indicate that reduction in LH pulse frequency such as that which occurs during the spontaneous menstrual cycle is not sufficient to promote luteal regression.

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