Ganong's Review of Medical Physiology, 23rd Edition

416 SECTION IV Endocrine & Reproductive Physiology
Cholesterol Pregnenolone 17α-Hydroxypregnenolone Dehydroepiandrosterone
HO
HO
FIGURE 25–26 Biosynthesis and metabolism of estrogens. The formulas of the precursor steroids are shown in Figure 22–7.
OVARIAN HORMONES
Chemistry, Biosynthesis, &
Metabolism of Estrogens
Progesterone
Estrone (E 1)
16-Ketoestrone
16α-Hydroxyestrone
Estriol (E 3)
The naturally occurring estrogens are 17β-estradiol, estrone,
and estriol (Figure 25–26). They are C18 steroids which do
not have an angular methyl group attached to the 10 position
or a Δ 4 -3-keto configuration in the A ring. They are secreted
primarily by the granulosa cells of the ovarian follicles, the corpus
luteum, and the placenta. Their biosynthesis depends on
the enzyme aromatase (CYP19), which converts testosterone
to estradiol and androstenedione to estrone (Figure 25–26).
The latter reaction also occurs in fat, liver, muscle, and the
brain.
Theca interna cells have many LH receptors, and LH acts via
cAMP to increase conversion of cholesterol to androstenedione.
The theca interna cells supply androstenedione to the
17α-Hydroxyprogesterone
O
OH
Aromatase Testosterone
OH
HO
Androstenedione
Aromatase
17β-Estradiol (E 2 )
granulosa cells. The granulosa cells make estradiol when provided
with androgens (Figure 25–27), and it appears that the
estradiol they form in primates is secreted into the follicular
fluid. Granulosa cells have many FSH receptors, and FSH facilitates
their secretion of estradiol by acting via cAMP to increase
their aromatase activity. Mature granulosa cells also acquire LH
receptors, and LH also stimulates estradiol production.
Two percent of the circulating estradiol is free, and the
remainder is bound to protein: 60% to albumin and 38% to
the same gonadal steroid-binding globulin (GBG) that binds
testosterone (Table 25–5).
In the liver, estradiol, estrone, and estriol are converted to
glucuronide and sulfate conjugates. All these compounds, along
with other metabolites, are excreted in the urine. Appreciable
amounts are secreted in the bile and reabsorbed into the bloodstream
(enterohepatic circulation).
Theca Interna
Granulosa
Circulation
Cells
Cells
Antrum
Cholesterol
Estradiol
Cholesterol
Androstenedione
Estrone
Androstenedione
FIGURE 25–27 Interactions between theca and granulosa cells in estradiol synthesis and secretion.
OH
Estrone Estradiol