Initiation of

Regression of corpus





degeneration luteum degeneration luteum

17a-hydroxyprogesterone rise dramatically after the LH surge and ovulation and peak at days 18-24 of the cycle; this is coincident with maximum steroid metabolism activity of the corpus luteum. The blood levels of both progesterone and estradiol fall after day 24 until the initiation of menstruation. If fertilization and implantation of the zygote occur (to be discussed later), hCG rescues the corpus luteum and stimulates the continued production of progesterone until the placenta becomes functional (see Chapter 14).

The mechanisms that govern the initiation of follicular growth as well as the selection of one follicle for the necessary maturation prior to ovulation are not clearly understood. This involves the sequence of maturation diagrammed in Figure 13-2. Important factors are the amount of LH and the ratio of FSH:LH; also, the availability of estrogen and possibly androgens is critical. In the immature female hypophysectomized rat model, estrogens clearly promote ovarian growth, reduce follicular atresia, induce granulosa cell hyperplasia, and increase ovarian response to FSH. In contrast, androgens in the same model promote follicular atresia. Thus, if LH were to stimulate androgen (andro-stenedione) production in certain follicles, or if there were differences in different secondary follicles of the ratio of estradiol to androgen combined with a favorable cellular receptor concentration for FSH, then one "selected" follicle would be stimulated to develop into a Graafian follicle. The Graafian follicle, in turn, would be subject to the influence of the gonadotropins and eventually ovulate.

Shown in Figure 13-2 is a pictorial representation of the developmental stages of follicular maturation and corpus luteum development in the ovary. In the selected secondary follicle on days 1-3 of the cycle, the oocyte becomes progressively larger and the surrounding granulosa cells proliferate further. The granulosa cells produce principally only estradiol. The cells adjacent to the follicle become enlarged and arranged in concentric circles; this cellular array is termed the thecal. The thecal cells are active in steroid metabolism and can produce both estradiol and andro-stenedione. As the follicle cell develops (days 6-10), the granulosa cells produce, as a consequence of the trophic actions of FSH, increasing amounts of estradiol. Blood levels of estradiol increase slowly (days 3-7) and then more rapidly to reach an apex (days 11-13) just prior to the LH surges. This has the effect of establishing the high levels of estradiol required for positive feedback at the CNS-hypothalamus and pituitary levels. Simultaneously, receptors for LH are appearing in increasing concentrations on both the thecal and granulosa cells in preparation for ovulation. Very late (days 11-13) in the follicular phase, the thecal cells are stimulated by LH to begin producing progesterone. By days 11-12 of the cycle the general maturation of the secondary follicle is complete, and it is referred to as a Graafian follicle. During this 12-day developmental process, the primary follicle has increased in size some 400 times from 50 to 29,000 /¿m, while the oogonium has increased some 10 times from 15 to 150 /an.

After ovulation, both the thecal and granulosa cells of the follicle undergo rapid mitosis. Capillaries are generated from the theca that invade the granulosa cells, thus creating a new endocrine organ, the corpus luteum. The corpus luteum reaches its maximum size within 2-8 days, and if fertilization and zygote implantation do not occur by 8-9 days, then it undergoes regression and degeneration, ultimately leading to the production of the corpus albicans. The corpus luteum, under the stimulus of LH, actively produces progesterone.

4. Changes in the Uterine Endometrium

The endometrium (see Figure 13-8) and vaginal epithelium undergo very striking morphological changes throughout the 28 days of the menstrual cycle. During the first half of each menstrual cycle, which is often denoted the follicular or preovulatory phase, the estrogen concentrations gradually increase to reach a maximum 24 hr before ovulation, while the progesterone concentrations are relatively low. These changes in estrogen, with a low progesterone value, stimulate the endometrium to increase in thickness from 1 to 3-5 mm. Then, 36 hr after ovulation, which signals the initiation of the luteal or postovulatory phase, the progesterone concentration rises sharply due to its secretion from the corpus luteum (see Figure 13-7). Simultaneously estrogen levels are maintained at levels two-thirds of their previous maximum. This balance of progesterone and estrogen induces further specific morphological changes in the endometrium. Glycogen-containing granules appear in the glandular cells; additionally, the glands of the endometrium become increasingly tortuous. This phase of the cycle is also termed the secretory phase since the lumens of the endometrial glands are filled with secretions. The endometrium also becomes highly vascularized with the ingrowth of new spiral arteries from the arcuate vessels of the myometrium. The growth of these spiral arteries is stimulated by estrogen.

In the event that fertilization and implantation do not occur, the stromal edema decreases, the glandular secretions diminish, and the endometrium is invaded by lymphocytes. The concentrations of estrogen and progesterone both fall sharply at days 27-28 of the cycle as a consequence of the involution of the corpus luteum. At the time of the rapid fall in estrogen and progesterone at the end of the luteal phase, the spiral arteries become constricted. Accordingly, blood flow through the capillaries supported by these arteries diminishes. Eventually blood stasis and stromal degeneration follow, and the endometrial tissue is sloughed off.

C. Menopause

Menopause is defined as the cessation of ovulation by the ovaries. This occurs in women between ages 40 and 50 years due to the utilization of the fixed number of follicles that were established in the fetal ovaries. Each month of ovulation, several follicles disappear by the process of atresia, and normally only one matures to contribute an ovum. Thus, at some interval in the fourth decade there are no more follicles available to support this cyclical process. The endocrinological consequences of cessation of ovulation are varied, and a variety of medical problems may develop, depending upon the exact nature of the reproductive hormonal balance achieved

In the postmenopausal woman, the average blood concentrations of FSH and LH remain elevated for the remainder of life. The postmenopausal secretion of immunoreactive LH is 7-fold higher and that of FSH is 3-fold higher than in a premenopausal woman. While the postmenopausal ovary is not totally devoid of the ability to secrete steroids, the production level is markedly reduced in comparison to a younger, ovulating woman. In menopausal women the major circulating estrogen is estrone; this is formed almost exclusively by aromatization of androstenedione by the adrenals as well as by adipose tissue and muscle. The control of LH and FSH secretion in postmenopausal women is mediated via a short feedback loop wherein FSH and LH themselves act on the hypothalamus in conjunction with steroids that are largely derived from the adrenals.

0 0

Post a comment