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chapter32
Endocrine Metabolism III: Adrenal Glands
Lysos°mey
C h0|es,ero0
Low-density
Cholesteryl
.£Ster storage
A c e ta te
Cytoplasm
De novo
synthesis
Receptor-mediated
endocytosis
LDL
lipoprotein
Mitochondrion
Rate-limiting
step mediated
by Star
Cholesterol
Cholesterol
side-cham
C o rtiso l
Cortisol
cleavage enzyme
(CYP11 A)
11 p-Hydroxylase
Pregnenolone
(CYP11B1)
11-Deoxycortisol
Endoplasmic
reticulum
Pregnenolone
3ß -Hydroxysteroid dehydrogenase
Progesterone
11-Deoxycortisol
117a-Hydroxylase (CYP17)
21-Hydroxylase
(CYP21 )
17a -Hydroxyprogesterone
FIGURE 32-2
Cortisol biosynthesis by mitochondrial and endoplasmic reticulum enzymes of the adrenal cortex. The rate-limiting step
in steroidogenesis is the importation of cholesterol from cytoplasm to mitochondria which is mediated by the
steroidogenic acute regulatory protein (StAR).
utilized mainly for formation of the androgen déhy-
droépiandrostérone (DHEA) and its sulfate (DHEAS),
which also requires
17a-hydroxylation (Figures 30-2
and 32-1). This hydroxylation is required for synthe-
sis of cortisol and androgens (and estrogens as well)
but not of aldosterone. Since the zona glomerulosa
lacks 17a-hydroxylase, it cannot synthesize cortisol or
androgens.
The adrenal cortex, the zona reticularis in particular,
daily secretes substantial amounts of DHEA and DHEAS,
equaling or exceeding the amount of cortisol. Table 32-1
shows approximate blood levels of the important corticos-
teroids. Most of the DHEA and all of the DHEAS come
from the adrenals. Negligible amounts of testosterone, di-
hydrotestosterone (DHT), and estradiol are secreted by the
cortex; however, DHEA and, to a lesser extent, DHEAS
undergo conversion to estradiol in skeletal muscle and adi-
pose tissue; they also can be converted to testosterone.
The adrenal cortex accounts for about two-thirds of the
urinary 17-ketosteroids, which are a measure of andro-
gen production. This steroidogenic versatility makes the
adrenal cortex an important factor in certain disease states
(see below).
Regulation of Corticosteroid Secretion
The zona glomerulosa and zona fasciculata differ in their
content of enzymes, major secretory products, and regu-
lators of their functions. They can be regarded as separate
endocrine tissues.
Regulation of Aldosterone Secretion
The major regulators of aldosterone secretion are the
renin-angiotensin system and extracellular potassium ions
(K+). The former is sensitive to changes in intravascu-
lar volume and arterial pressure, while the latter is an
aldosterone-regulated substance that feeds back to reduce
aldosterone synthesis (simple negative feedback). Aldos-
terone secretion is also influenced (but not regulated) by
ACTH and, directly and indirectly, by atrial natriuretic
factor (ANF).
Potassium ions exert a direct, stimulatory effect on
aldosterone secretion that is independent of the renin-
angiotensin system. Small increases in serum potassium
elicit a rise in serum aldosterone levels, whereas small
decreases in serum potassium result in reduced levels
of serum aldosterone. Aldosterone, by promoting the
