CHAPTER 22
The Adrenal Medulla & Adrenal Cortex 343hydroxyl group at the 17 position in addition to the side chain are
often called 17-hydroxycorticoids or 17-hydroxycorticosteroids.
The C
19
steroids have androgenic activity. The C
21
steroids
are classified, using Selye’s terminology, as mineralocorticoids
or glucocorticoids. All secreted C
21
steroids have both miner-
alocorticoid and glucocorticoid activity;
mineralocorticoids
are those in which effects on Na
- and K
excretion predomi-
nate and
glucocorticoids
are those in which effects on glu-
cose and protein metabolism predominate.
The details of steroid nomenclature and isomerism can be
found elsewhere. However, it is pertinent to mention that the
Greek letter
Δ
indicates a double bond and that the groups that
lie above the plane of each of the steroid rings are indicated by
the Greek letter
α
and a solid line (—OH), whereas those that lie
below the plane are indicated by
α
and a dashed line (- - -OH).
Thus, the C
21
steroids secreted by the adrenal have a
Δ
4
-3-keto
configuration in the A ring. In most naturally occurring adrenal
steroids, 17-hydroxy groups are in the
α
configuration, whereas
3-, 11-, and 21-hydroxy groups are in the
β
configuration. The
18-aldehyde configuration on naturally occurring aldosterone is
the D form.
L
-Aldosterone is physiologically inactive.
SECRETED STEROIDS
Innumerable steroids have been isolated from adrenal tissue,
but the only steroids normally secreted in physiologically sig-
nificant amounts are the mineralocorticoid
aldosterone,
the
glucocorticoids
cortisol
and
corticosterone,
and the andro-
gens
dehydroepiandrosterone (DHEA)
and
androstenedi-
one.
The structures of these steroids are shown in Figures 22–7
and 22–8.
Deoxycorticosterone
is a mineralocorticoid that is
normally secreted in about the same amount as aldosterone
(Table 22–1) but has only 3% of the mineralocorticoid activity
of aldosterone. Its effect on mineral metabolism is usually neg-
ligible, but in diseases in which its secretion is increased, its ef-
fect can be appreciable. Most of the estrogens that are not
formed in the ovaries are produced in the circulation from ad-
renal androstenedione. Almost all the dehydroepiandrosterone
is secreted conjugated with sulfate, although most if not all of
the other steroids are secreted in the free, unconjugated form.
The secretion rate for individual steroids can be determined
by injecting a very small dose of isotopically labeled steroid
and determining the degree to which the radioactive steroid
excreted in the urine is diluted by unlabeled secreted hor-
mone. This technique is used to measure the output of many
different hormones (see Clinical Box 22–1).SPECIES DIFFERENCES
In all species from amphibia to humans, the major C
21
steroid
hormones secreted by adrenocortical tissue appear to be aldos-
terone, cortisol, and corticosterone, although the ratio of cortisol
to corticosterone varies. Birds, mice, and rats secrete corticoster-
one almost exclusively; dogs secrete approximately equal
amounts of the two glucocorticoids; and cats, sheep, monkeys,
and humans secrete predominantly cortisol. In humans, the ra-
tio of secreted cortisol to corticosterone is approximately 7:1.FIGURE 22–7
Outline of hormone biosynthesis in the zona fasciculata and zona reticularis of the adrenal cortex.
The major secreto-
ry products are underlined. The enzymes for the reactions are shown on the left and at the top of the chart. When a particular enzyme is deficient,
hormone production is blocked at the points indicated by the shaded bars.
COOCH 2 OHCO
HOOCH 2 OHCorticosterone11-Deoxy-
corticosteroneCOOCH 3ProgesteroneCOHOCH 3PregnenoloneACTHCOOCH 2 OHCO
HOOCH 2 OHCOOCH 3CO
OHHOCH 317-Hydroxy-
pregnenolone17-Hydroxy-
progesterone11-DeoxycortisolCortisolCholesterolCholesterol
desmolase3 β-Hydroxysteroid
dehydrogenase17 α-Hydroxylase 17,20-Lyase21 β-Hydroxylase11 β-HydroxylaseOHOOHO
ODehydroepiandros-
teroneAndrostenedioneTestosteroneEstradiolOHOHSulfo-
kinase DHEA
sulfate