Fig. 44.22 ) increases steadily from the onset of the LH surge and peaks during the midluteal phase. The main purpose of this timing is to transform the uterine lining into an adhesive and supportive structure for implantation and early pregnancy. As discussed later the midluteal phase is synchronized with early embryogenesis so the uterus is optimally primed when a blastocyst tumbles into the uterus around day 22 of the menstrual cycle. Estradiol continues to be produced by theca lutein cells and granulosa lutein cells. Estrogen production transiently decreases in response to the LH surge but then rebounds and peaks at the midluteal phase. Estradiol induces the progesterone receptor in progesterone target cells, such as the uterine endometrium, and ensures a full response to progesterone.
Luteal hormonal output is absolutely dependent on basal LH levels (see
Fig. 44.22 ). In fact, progesterone output is closely correlated with the pulsatile pattern of LH release in women. Both FSH and LH are reduced to basal levels during the luteal phase by negative feedback from progesterone and estrogen. In addition, granulosa lutein cells secrete inhibin, which selectively represses FSH secretion.
The corpus luteum must generate large amounts of progesterone to support implantation and early pregnancy. Accordingly the life of the corpus luteum is very regular, and a shortened luteal phase typically leads to infertility. The quality of the corpus luteum is largely dependent on the size and health of the dominant follicle from which it developed, which in turn is dependent on normal hypothalamic and pituitary stimulation during the follicular phase. Numerous factors that perturb hypothalamic and pituitary output during the follicular phase, including heavy exercise, starvation, high prolactin levels, and abnormal thyroid function, can lead to luteal phase deficiency and infertility.
Follicular atresia refers to the demise of an ovarian follicle. During atresia the granulosa cells and oocytes undergo apoptosis. The thecal cells typically persist and repopulate the cellular stroma of the ovary. The thecal cells retain LH receptors and the ability to produce androgens and are collectively referred to as the “interstitial gland” of the ovary. Follicles can undergo atresia at any time during development.
Follicular Development With Respect to the Monthly Menstrual Cycle
The human menstrual cycle strictly refers to the monthly discharge of discarded uterine lining as menstrual blood or menstrual flow (a period referred to as menses) through the process of menstruation (see later). In fact it is the onset or lack thereof of menses, as detected by the woman herself, that is the primary evidence for the cessation of menstruation (e.g., due to pregnancy or menopause) or a change in the duration and/or frequency of the menstrual cycle. However, it is useful from an endocrinological perspective to consider the human menstrual cycle as having an ovarian cycle and a uterine cycle, with the latter being driven by the former. As discussed later, there are also hypothalamic, pituitary, oviductal, and vaginal components of the human menstrual cycle. The reproductive function of the menstrual cycle is the collective orchestration by ovarian hormones of the functions of the hypothalamus, pituitary, uterus, oviduct, cervix, and vagina—and even the ovary itself—to: (1) produce a fertilizable gamete (egg), (2) provide a supportive environment for intercourse, reception of sperm, fertilization of egg and early embryogenesis, (3) prepare the uterine lining for implantation, placentation and pregnancy, and (4) minimize the possibility of a superimplantation (i.e., a second implantation) from occurring, and/or prevent an ascending infection from moving up to the uterus from the vagina.