- Estrogens, which regulate ovulation and the development of the secondary female
sex characteristics - Progestins, or gestagens, which maintain pregnancy
- Androgens, the male sex hormone
These three classes of sex hormones are of fundamental importance in medicinal chem-
istry, not only for their role in influencing reproductive susceptibilities, but also as
potential therapeutics in a range of other conditions, including cancer.
5.8 STEROID HORMONES: SEX HORMONES—ESTROGENS
Of these three classes of sex steroid hormones, the estrogens are the best studied.
Estrogens are produced mainly in the ovaries when the latter are stimulated by follicle-
stimulating hormone (FSH). Under such stimulation, the estrogen levels rise until the
middle of the menstrual cycle (when ovulation takes place), remain at a fairly constant
concentration, and then decline if fertilization does not take place. The final result is
menses, the shedding of the uterine endometrium (lining). Estrogens also regulate
uterine growth in immature animals and, as noted above, are responsible for all female
secondary sex characteristics.
5.8.1 Naturally Occurring and Synthetic Steroidal EstrogensThe major estrogens produced by women are estrone (5.22,E 1 ), estradiol (5.23,
17 β-estradiol, E 2 ), and estriol (5.24,E 3 ). Estradiol is the major secretory product of the
ovary. Estrone and estriol are formed either in the liver, from estradiol, or in peripheral
tissues, from androgens such as androstenedione. During the first part of the menstrual
cycle, estrogens are produced in the ovarian follicles (80–350 μg/day estradiol); after
ovulation, estrogens are synthesized (via a different biosynthetic pathway) in the
corpus luteum, which is a proliferation of cells that replace clotted blood within the
ruptured ovarian follicle. During pregnancy, large amounts of estrogen are synthesized
by the fetoplacental unit (1000-fold increase when compared to the nonpregnant state).
Estriol synthesized by the fetoplacental unit enters the maternal circulation and is
excreted in the urine.
Although estrogens are easily isolated from the urine of pregnant women, their most
abundant source has historically been from the urine of horses, especially pregnant
mares. Somewhat surprisingly, however, the most prolific source of estrogen is stal-
lions, in which urinary estrogens are produced as metabolites of androgens. Horses
HORMONES AND THEIR RECEPTORS 321