Ganong's Review of Medical Physiology, 23rd Edition

416 SECTION IVEndocrine & Reproductive Physiology

OVARIAN HORMONES

Chemistry, Biosynthesis, &

Metabolism of Estrogens

The naturally occurring estrogens are 17 β-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 cor-
pus 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 androstenedi-
one. The theca interna cells supply androstenedione to the

granulosa cells. The granulosa cells make estradiol when pro-

vided 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 facili-

tates 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 blood-

stream (enterohepatic circulation).

FIGURE 25–26 Biosynthesis and metabolism of estrogens. The formulas of the precursor steroids are shown in Figure 22–7.

HO

O

HO

OH

HO

OH

Estrone (E 1 )

17 β-Estradiol (E 2 )

Estriol (E 3 )

16-Ketoestrone

16 α-Hydroxyestrone

OH

Aromatase

Aromatase Testosterone

17 α- Hydroxyprogesterone Androstenedione

17 α- Hydroxypregnenolone

Progesterone

Cholesterol Pregnenolone Dehydroepiandrosterone

FIGURE 25–27 Interactions between theca and granulosa cells in estradiol synthesis and secretion.

Theca Interna

Cells

Cholesterol Cholesterol

Androstenedione

Estrone

Granulosa

Circulation Cells Antrum

Androstenedione

Estradiol Estrone Estradiol