Page 736 - Basic _ Clinical Pharmacology ( PDFDrive )

722 SECTION VII Endocrine Drugs

self-limited. They are often associated with emotional or physical those found in ocean sediments. Estrogen-mimetic compounds
stress and reflect temporary alterations in the stress centers in the (flavonoids) are found in many plants, including saw palmetto,
brain that control the secretion of GnRH. Anovulatory cycles are and soybeans and other foods. A diet rich in these plant prod-
also associated with eating disorders (bulimia, anorexia nervosa) ucts may cause slight estrogenic effects. Additionally, some
and with severe exercise such as distance running and swimming. compounds used in the manufacture of plastics (bisphenols,
Among the more common organic causes of persistent ovulatory alkylphenols, phthalate phenols) have been found to be estro-
disturbances are pituitary prolactinomas and syndromes and genic. It has been proposed that these agents are associated
tumors characterized by excessive ovarian or adrenal androgen with an increased breast cancer incidence in both women and
production. Normal ovarian function can be modified by andro- men in the industrialized world.
gens produced by the adrenal cortex or tumors arising from it.
The ovary also gives rise to androgen-producing neoplasms such Natural Estrogens
as arrhenoblastomas, as well as to estrogen-producing granulosa
cell tumors. The major estrogens produced by women are estradiol (estradiol-
17β, E ), estrone (E ), and estriol (E ) (Figure 40–2). Estradiol
2
3
1
THE ESTROGENS is the major secretory product of the ovary. Although some
estrone is produced in the ovary, most estrone and estriol are
Estrogenic activity is shared by a large number of chemical sub- formed in the liver from estradiol or in peripheral tissues from
stances. In addition to the variety of steroidal estrogens derived androstenedione and other androgens (see Figure 39–1). As
from animal sources, numerous nonsteroidal estrogens have noted above, during the first part of the menstrual cycle estro-
been synthesized. Many phenols are estrogenic, and estrogenic gens are produced in the ovarian follicle by the theca and granu-
activity has been identified in diverse forms of life including losa cells. After ovulation, the estrogens as well as progesterone

Follicular phase Luteal phase
Pregnenolone Pregnenolone

17α-Hydroxypregnenolone Progesterone

Dehydroepiandrosterone 17α-Hydroxyprogesterone

18 O OH
H C H C
3
3
12 17
19 11 13 16
H C 14 15 H C
3
3
1 9
2 10 8
3 4 5 6 7
O O
Androstenedione Testosterone
Aromatase
OH O O OH
H C H C H C H C
3
3
3
3
OH OH
C D
A B
HO HO HO HO
Estriol 16α-Hydroxyestrone Estrone 17β-Estradiol

2-Hydroxyestrone 2-Hydroxyestradiol
and other metabolites and other metabolites
FIGURE 40–2 Biosynthesis and metabolism of estrogens and testosterone.