Luteal Phase Structure of Corpus Luteum After ovulation, the remaining follicular shell is transformed into the primary regulator of the luteal phase: the corpus luteum. Membranous granulosa cells remaining in the follicle begin to take up lipids and the characteristic yellow lutein pigment for which the structure is named. These cells are active secretory structures that produce progesterone, which supports the endometrium of the luteal phase. In addition, estrogen and inhibin-A are produced in significant quantities. Unlike the process that occurs in the developing follicle, the basement membrane of the corpus luteum degenerates to allow proliferating blood vessels to invade the granulosa-luteal cells in response to secretion of angiogenic factors such as vascular endothelial growth factor (97). This angiogenic response allows large amounts of luteal hormones to enter the systemic circulation.
Hormonal Function and Regulation The hormonal changes of the luteal phase are characterized by a series of negative feedback interactions designed to lead to regression of the corpus luteum if pregnancy does not occur. Corpus luteum steroids (estradiol and progesterone) provide negative central feedback and cause a decrease in FSH and LH secretion. Continued secretion of both steroids will decrease the stimuli for subsequent follicular recruitment. Similarly, luteal secretion of inhibin also potentiates FSH withdrawal. In the ovary, local production of progesterone inhibits the further development and recruitment of additional follicles.
Continued corpus luteum function depends on continued LH production. In the absence of this stimulation, the corpus luteum will invariably regress after 12 to 16 days and form the scarlike corpora albicans (98). The exact mechanism of luteolysis is unclear and most likely involves local paracrine factors. In the absence of pregnancy, the corpus luteum regresses, and estrogen and progesterone levels wane. This, in turn, removes central inhibition on gonadotropin secretion and allows FSH and LH levels to again rise and recruit another cohort of follicles.
If pregnancy does occur, placental hCG will mimic LH action and continually stimulate the corpus luteum to secrete progesterone. Successful implantation results in hormonal support to allow continued maintenance of the corpus luteum and the endometrium. Evidence from patients undergoing oocyte donation cycles demonstrated that continued luteal function is essential to continuation of the pregnancy until approximately 5 weeks of gestation, when sufficient progesterone is produced by the developing placenta (99). This switch in the source of regulatory progesterone production is referred to as the luteal–placental shift.
Summary of Menstrual Cycle Regulation
Following is a summary of the regulation of the menstrual cycle: 1.
GnRH is produced in the arcuate nucleus of the hypothalamus and secreted in a pulsatile fashion into the portal circulation, where it travels to the anterior pituitary.
2.
Ovarian follicular development moves from a period of gonadotropin independence to a phase of FSH dependence.
3.
As the corpus luteum of the previous cycle fades, luteal production of progesterone and inhibin-A decreases, allowing FSH levels to rise.
4.
In response to FSH stimulus, the follicles grow, differentiate, and secrete increasing amounts of estrogen and inhibin-B.
5.
Estrogen stimulates growth and differentiation of the functional layer of the endometrium, which prepares for implantation. Estrogens work with FSH in stimulating follicular development.
6.
The two-cell, two-gonadotropin theory dictates that with LH stimulation, the ovarian theca cells will produce androgens that are converted by the granulosa cells into estrogens under the stimulus of FSH.
7.
Rising estrogen and inhibin levels negatively feed back on the pituitary gland and hypothalamus and decrease the secretion of FSH.