Ganong's Review of Medical Physiology, 23rd Edition

344
SECTION IV
Endocrine & Reproductive Physiology

STEROID BIOSYNTHESIS

The major paths by which the naturally occurring adrenocortical

hormones are synthesized in the body are summarized in Fig-

ures 22–7 and 22–8. The precursor of all steroids is cholesterol.

Some of the cholesterol is synthesized from acetate, but most of

it is taken up from LDL in the circulation. LDL receptors are es-

pecially abundant in adrenocortical cells. The cholesterol is es-

terified and stored in lipid droplets.

Cholesterol ester hydrolase

catalyzes the formation of free cholesterol in the lipid droplets

(Figure 22–9). The cholesterol is transported to mitochondria by

a sterol carrier protein. In the mitochondria, it is converted to

pregnenolone in a reaction catalyzed by an enzyme known as

cholesterol desmolase

or

side-chain cleavage enzyme.

This en-

zyme, like most of the enzymes involved in steroid biosynthesis,

is a member of the cytochrome P450 superfamily and is also

known as

P450scc

or

CYP11A1.

For convenience, the various

FIGURE 22–8
Hormone synthesis in the zona glomerulosa.
The zona glomerulosa lacks 17
α
-hydroxylase activity, and only the
zona glomerulosa can convert corticosterone to aldosterone because
it is the only zone that normally contains aldosterone synthase. ANG II,
angiotensin II.

TABLE 22–1
Principal adrenocortical
hormones in adult humans.a

Name Synonyms

Average Plasma

Concentration

(Free and

Bound)a

(μg/dL)

Average

Amount

Secreted

(mg/24 h)

Cortisol Compound F,

hydrocortisone

13.9 10

Corticosterone Compound B 0.4 3

Aldosterone 0.0006 0.15

Deoxycorticos-

terone

DOC 0.0006 0.20

Dehydroepi-

androsterone

sulfate

DHEAS 175.0 20

aAll plasma concentration values except DHEAS are fasting morning values after
overnight recumbency.

CO

HO

HO

O

CH 2 OH

CH 2

CO

O

HO HC

O

CH 2 OH

Cortisol

and

sex steroids

Cholesterol

Pregnenolone

Progesterone

Deoxycorticosterone

Corticosterone

18-Hydroxycorticosterone

Aldosterone

Aldosterone

synthase

Aldosterone

synthase

ANG II

Aldosterone

synthase

ACTH

ANG II

CLINICAL BOX 22–1

Synthetic Steroids

As with many other naturally occurring substances, the ac-

tivity of adrenocortical steroids can be increased by alter-

ing their structure. A number of synthetic steroids are avail-

able that have many times the activity of cortisol. The

relative glucocorticoid and mineralocorticoid potencies of

the natural steroids are compared with those of the syn-

thetic steroids 9α-fluorocortisol, prednisolone, and dexa-

methasone in Table 22–2. The potency of dexamethasone

is due to its high affinity for glucocorticoid receptors and its

long half-life. Prednisolone also has a long half-life.

TABLE 22–2 Relative potencies of

corticosteroids compared with cortisol.a

Steroid

Glucocorticoid

Activity

Mineralocorticoid

Activity

Cortisol 1.0 1.0

Corticosterone 0.3 15

Aldosterone 0.3 3000

Deoxycorticosterone 0.2 100

Costisone 0.7 0.8

Prednisolone 4 0.8

9 α-Fluorocortisol 10 125

Dexamethasone 25 –0

aValues are approximations based on liver glycogen deposition or anti-inflamma-

tory assays for glucocorticoid activity, and effect on urinary Na+/K+ or maintenance

of adrena-lectomized animals for mineralocorticoid activity. The last three steroids

listed are synthetic compounds that do not occur naturally.