Event 6 occurs during the late follicular phase (Fig. 44.23A). When estrogen levels in women surpass 200 pg/mL for approximately 50 hours due to the dominant follicle, a positive feedback is triggered on the gonadotrope, resulting in the midcycle LH surge. This feedback is enhanced by a small amount of progesterone secreted at midcycle. Although the precise mechanism of this positive feedback is not fully understood, it primarily occurs at the level of the pituitary. The gonadotropes experience a significant increase in GnRH receptors and sensitivity to GnRH signaling. Additionally, the hypothalamus contributes to the gonadotropin surge by increasing the frequency of GnRH pulses.

Event 7, which takes place during the late follicular phase (Fig. 44.23A), is driven by the LH surge. This surge is responsible for meiotic maturation, ovulation, and the transformation of granulosa cells into progesterone-producing cells.

Following the LH surge, event 8 occurs during the mid-luteal phase (Fig. 44.23B). The mature corpus luteum leads to rising levels of progesterone, estrogen, and inhibin A, which exert negative feedback on pituitary gonadotropes. Although estradiol levels exceed the threshold for positive feedback (200 pg/mL), the high levels of progesterone produced by the corpus luteum block any positive feedback of estradiol. Consequently, both FSH and LH levels decrease to basal levels.

Event 9, which is vital for normal corpus luteum function, takes place during the late luteal phase (Fig. 44.23B). Basal levels of LH (but not FSH) are essential. However, the corpus luteum progressively becomes less responsive to LH signaling and will degenerate unless there is an increase in LH-like activity, such as hCG from an implanted embryo. In a nonfertile cycle, the corpus luteum will regress in 14 days, and levels of progesterone and estrogen will begin to decline around day 10, leading back to event 1.
Fig. 44.23A , Late Follicular Phase).
Event 6: Once the dominant follicle causes circulating estrogen levels to exceed 200 pg/mL for about 50 hours in women, estrogen exerts a positive feedback on the gonadotrope to produce the midcycle LH surge. This is enhanced by the small amount of progesterone secreted at midcycle. The exact mechanism of the positive feedback is unknown, but it occurs largely at the level of the pituitary. GnRH receptors and the sensitivity to GnRH signaling increase dramatically in the gonadotropes. The hypothalamus contributes to the gonadotropin surge by increasing the frequency of GnRH pulses.
Event 7: The LH surge drives meiotic maturation, ovulation, and differentiation of granulosa cells into progesterone-producing cells (see
Fig. 44.23A , Late Follicular Phase).
Event 8: Rising levels of progesterone, estrogen, and inhibin A by the mature corpus luteum negatively feed back on pituitary gonadotropes. Even though estradiol levels exceed the 200-pg/mL threshold for positive feedback, the high progesterone levels now produced by the corpus luteum block any positive feedback of estradiol. Consequently both FSH and LH levels decline to basal levels (see
Fig. 44.23B , Mid-Luteal Phase).
Event 9: Basal levels of LH (but not FSH) are absolutely required for normal corpus luteum function. However, the corpus luteum becomes progressively insensitive to LH signaling and will die unless LH-like activity (i.e., hCG from an implanted embryo) increases. In a nonfertile cycle the corpus luteum of menstruation will regress in 14 days, and progesterone and estrogen levels will start to decline by about 10 days, thereby cycling back to event 1 (see
Fig. 44.23B , Late Luteal Phase).