Page 274 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Adrenocortical Hormones: Enzyme Defects in Formation
The most important adrenocortical hormones By using ACTH to stimulate adrenocorticoid
(corticoids) are the glucocorticoids and miner- hormone production, glucococorticoid pro-
alocorticoids. Androgens, progestogens, and duction can be (practically) normalized, in
estrogens are also formed in the adrenal cor- spite of an enzyme defect. More frequently,
tex. though, the glucocorticoid action decreases
All adrenocortical hormones (see also (→ p. 270). If there is an excess of gestagenic
p. 272ff.) are formed from cholesterol. The metabolites, their weak antimineralocorticoid
transport of cholesterol to the mitochondria effect can trigger natriuresis (→ p. 276). Some
and subsequent transformation in pregneno- enzyme defects increase concentrations of an-
lone can be impaired by a deficiency in ste- drogenic metabolites, with the corresponding
roidogenic acute regulatory protein (StAR). consequences for sexual development
Several enzymes, which may be absent in ge- (→ p. 272f.). If there is a 3β-hydroxydehydro-
netic defects, are necessary for the formation genase defect (→ A3), then insufficient
of the various hormones. amounts of androgens are formed for normal
Enzyme defects lead to decreased synthesis male sexual development to take place; too
of enzyme products, and thus also of the hor- many androgens are formed for normal female
Hormones reduced glucocorticoid synthesis leads to dis- of the sexual hormones in the adrenal cortex
sexual development. Limiting the production
mones formed through their action. However,
does not, however, generally impair sexual de-
inhibition of the formation of corticoliberins
pic hormone [ACTH]). Corticotropin, in turn,
mally mainly formed in the gonads.
9 (CRH) and of corticotropin (adrenocorticotro- velopment, since the sexual hormones are nor-
stimulates the growth of the adrenal cortex, The most common enzyme defect is a
the release of cholesterol and the expression deficiency of 21β-hydroxylase (cytochrome
of several enzymes involved in the synthesis P450c21). Such a deficiency impairs transfor-
of adrenocorticoid hormones. As a result of mation of progesterone into 11-desoxycorti-
this action, there is a rise in the concentration costerone and of 17-hydroxyprogesterone into
of enzyme substrates, their precursors, and 11-desoxycortisol (→ A5). Depending on the
metabolites as well as of steroids which are ac- extent to which enzyme activity is impaired,
tive preceding the enzyme defect in the meta- there will be a moderate to severe cortisol de-
bolic chain. These steroids have partly hor- ficiency. Increased formation of androstendion
monal effects, namely glucocorticoid (blue), and testosterone leads to virilization of girls
mineralocorticoid (green), androgenic (red), and premature development of male sex char-
progestogenic (orange), and estrogenic (violet) acteristics (incomplete precocious puberty) in
ones, as illustrated in Figs. 9.7–9.10. Depend- boys (adrenogenital syndrome; see also
ing on what activity those products, sub- p. 272). These effects can already be detected
strates, precursors, and metabolites possess, at birth, since the excess androgens are formed
there may thus be reduced (↓) or increased intrauterinely.
(↑) hormonal effects (see Table).

Enzym Defect Androgenic Glucocorticoid Mineralcorticoid
(→ A1–8) Action Action Action
! 20,22-Desmolase (P450scc, StAR) ↓ ↓ ↓
" 17α-Hydroxylase (P450c17) ↓ ↓ ↑
# 3β-Hydroxydehydrogenase ↑ (,) ↓ (<) ↓ ↓
$ 17-Reductase ↓ – –
% 21β-Hydroxylase (P450c21) ↑ ↓ ↓
& 11β-Hydroxylase (P450c11) ↑ ↓ ↑
264 ' 18-Hydroxylase (P450c11AS) – – ↓
( 18-Methyloxidase (P450c11AS) – – ↓
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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