Page 735 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 40 The Gonadal Hormones & Inhibitors 721

A CR ON Y MS a corpus albicans. The endometrium, which proliferated during
the follicular phase and developed its glandular function during
CBG Corticosteroid-binding globulin (transcortin)
the luteal phase, is shed in the process of menstruation. These
DHEA Dehydroepiandrosterone events are summarized in Figure 40–1.
DHEAS Dehydroepiandrosterone sulfate The ovary normally ceases its gametogenic and endocrine
ERE Estrogen response element function with time. This change is accompanied by a cessation
FSH Follicle-stimulating hormone in uterine bleeding (menopause) and occurs at a mean age of
52 years in the United States. Although the ovary ceases to secrete
GnRH Gonadotropin-releasing hormone
estrogen, significant levels of estrogen persist in many women as a
HDL High-density lipoprotein
result of conversion of adrenal and ovarian steroids such as andro-
HRT Hormone replacement therapy (also called HT) stenedione to estrone and estradiol in adipose and possibly other
LDL Low-density lipoprotein nonendocrine tissues.
LH Luteinizing hormone
PRE Progesterone response element A. Disturbances in Ovarian Function
SERM Selective estrogen receptor modulator Disturbances of cyclic function are common even during the peak
years of reproduction. A minority of these result from inflam-
SHBG Sex hormone-binding globulin
matory or neoplastic processes that influence the functions of
TBG Thyroxine-binding globulin
the uterus, ovaries, or pituitary. Many of the minor disturbances
leading to periods of amenorrhea or anovulatory cycles are
small amounts of the latter two hormones are released during the
night, and the limited quantities of ovarian estrogen secreted in Follicular development
response start to cause breast development. Subsequently, FSH
and LH are secreted throughout the day and night, causing secre-
tion of higher amounts of estrogen and leading to further breast
enlargement, alterations in fat distribution, and a growth spurt
that culminates in epiphyseal closure in the long bones. The
change of ovarian function at puberty is called gonadarche. Endometrium
A year or so after gonadarche, sufficient estrogen is produced
to induce endometrial changes and periodic bleeding (menarche).
After the first few irregular cycles, which may be anovulatory,
normal cyclic function is established. 0 7 14 21 28
At the beginning of each cycle, a variable number of follicles Days
(vesicular follicles), each containing an ovum, begin to enlarge 80
in response to FSH. After 5 or 6 days, one follicle, called the Gonadotropins
dominant follicle, begins to develop more rapidly. The outer 60
theca and inner granulosa cells of this follicle multiply and,
under the influence of LH, synthesize and release estrogens at 40
an increasing rate. The estrogens appear to inhibit FSH release mIU/mL
and may lead to regression of the smaller, less mature follicles. LH FSH
The mature dominant ovarian follicle consists of an ovum sur- 20
rounded by a fluid-filled antrum lined by granulosa and theca
cells. The estrogen secretion reaches a peak just before midcycle, 0
and the granulosa cells begin to secrete progesterone. These 400
changes stimulate the brief surge in LH and FSH release that Estradiol
precedes and causes ovulation. When the follicle ruptures, the pg/mL 200
ovum is released into the abdominal cavity near the opening of
the uterine tube. 0
Following the above events, the cavity of the ruptured fol- 20
licle fills with blood (corpus hemorrhagicum), and the lutein- Progesterone
ized theca and granulosa cells proliferate and replace the blood ng/mL
to form the corpus luteum. The cells of this structure produce
estrogens and progesterone for the remainder of the cycle, or 0
longer if pregnancy occurs. 1 7 14 21 28
If pregnancy does not occur, the corpus luteum begins to FIGURE 40–1 The menstrual cycle, showing plasma levels of
degenerate and ceases hormone production, eventually becoming pituitary and ovarian hormones and histologic changes.