the sensitivity of target cells, as well as by changes in concentration of a stimulatory hormone. Women and experimental animals are more responsive to a test dose of GnRH at midcycle than at any other time. An increase in the number of receptors for GnRH at this time has been reported, and there is evidence that the high concentrations of estradiol that precede the LH surge upregulate GnRH receptors and stimulate LH synthesis and storage.
Although the pacemaker for rhythmic release of GnRH resides in the hypothalamus, the timekeeper for the slower monthly rhythm of the ovarian cycle resides in the ovary. As already indicated, the corpus luteum has a built-in life-span of about 12 days and involutes despite continued stimulation with LH. A new cohort of follicles cannot arise as long as the corpus luteum remains functional. Its demise appears to relieve inhibition of follicular growth and secretion of FSH, which increases sufficiently in blood to stimulate growth of the next cohort of follicles. Thus, the interval between the LH surge and the emergence of the new cohort of follicles is determined by the ovary. The principal event around which the menstrual cycle revolves is ovulation, which depends on an ovulatory surge of LH. The length of the follicular phase may be somewhat variable and may be influenced by extraovarian events, but the timing of the LH surge resides in the ovary. It is only when the developing follicle signals its readiness to ovulate with increasing blood levels of estradiol that the pituitary secretes the ovulatory spike of gonadotropin. Hence throughout the cycle it is the ovary that notifies the pituitary and hypothalamus of its readiness to proceed to the next stage.
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