Page 307 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Biosynthesis of Steroid Hormones p. 182) can be synthesized. Initial hydroxyla-
tion at C17 (! A, f or g) results in the synthesis
Cholesterol is the precursor of steroid hor- of glucocorticoids—realized mainly in the
mones (! A). Cholesterol is mainly synthe- fascicular zone of the adrenal cortex (! A, h ! j
sized in the liver. It arises from acetyl- ! k)—and 17-ketosteroids, steroids with a
coenzyme A (acetyl-CoA) via a number of in- keto group at C17 (! A, l and m). Glucocorti-
termediates (e.g., squalene, lanosterol) and is coids and 17-ketosteroids can therefore be
transported to the endocrine glands by lipo- synthesized from 17α-hydroxypregnenolone
proteins (! p. 256). Cholesterol can be synthe- without the aid of progesterone (! A, n ! h !
sized de novo also in the adrenal cortex, but j). The estrogens (! p. 302) estrone and
Hormones and Reproduction ovaries, testes and placenta (! p. 304), they are produced indirectly by way of testosterone
not in the placenta (! p. 304). Since only small
estradiol can be directly or indirectly synthe-
quantities of steroid hormones are stored in
sized from 17-ketosteroids (! A, o ! p); they
the organs of origin, i.e., the adrenal cortex,
cellular
the
(! A, q ! r ! p). The true active substance of
must
be
synthesized
from
certain target cells for androgens (e.g., in the
cholesterol pool as needed.
prostate) is either dihydrotestosterone or
Cholesterol contains 27 carbon atoms. Preg-
estradiol ; both are synthesized from testo-
nenolone (21 C atoms; ! A, a), the precursor of
sterone (! A,s and A,r, respectively).
steroid hormones, arises from cholesterol via
yields progesterone (! A, b), which is not
(testes and ovaries) and adrenal cortex. Since they
only a potent hormone itself (female sex hor-
are found in the urine, the metyrapone test of pitui-
11 numerous intermediates. Pregnenolone also 17-ketosteroids are synthesized by the gonads
mone; ! p. 298ff.), but can act as the precursor
tary function is used to assess the ACTH reserve based
of all other steroid hormones, i.e., (1) the on urinary 17-ketosteroids levels. ACTH secretion is
adrenocortical hormones with 21 carbon normally subject to feedback control by glucocorti-
atoms (! A, yellow and orange fields); (2) coids (! p. 296). Metyrapone inhibits 11-hydroxy-
male sex hormones (androgens, 19 carbon lase activity (! A, d and j), which leaves ACTH un-
atoms) synthesized in the testes (! p. 306), suppressed in healthy subjects. Urinary 17-ke-
tosteroid levels should therefore increase after mety-
ovaries and adrenal cortex (! A, green and rapone administration. An abnormality of ACTH
blue fields); and (3) female sex hormones secretion can be assumed when this does not occur
(estrogens, 18 carbon atoms; ! p. 29 B ff.) syn- in patients with a healthy adrenal cortex.
thesized in the ovaries (! A, red zones).
The precursors for steroid hormone synthe- Degradation of steroid hormones occurs
sis are present in all steroid hormone glands. mainly in the liver. Their OH groups are usually
The type of hormone produced and the site of linked to sulfate or glucuronic acid molecules
hormone synthesis depend on (1) the type of and are ultimately excreted in the bile or urine
receptors available for the superordinate con- (! pp. 160, 183 and 250). The chief urinary
trol hormones (ACTH, FSH, LH, etc.) and (2) the metabolite of the estrogens is estriol, while
dominant enzyme responsible for changing that of the gestagens (mainly progesterone
the structure of the steroid molecule in the and 17α-hydroxyprogesterone) is pregnane-
hormone-producing cells of the gland in ques- diol (! p. 304). Pregnanediol levels in urine
tion. The adrenal cortex contains 11-, 17- and can be measured to confirm or exclude preg-
21-hydroxylases—enzymes that introduce an nancy test (pregnanediol test). Chronically in-
OH group at position C21, C17 or C11, respec- creased estrogen levels due, for example, to
tively, of the steroid molecule (! A, top left decreased estrogen degradation secondary to
panel for numerical order). Hydroxylation at liver damage, can lead to breast development
C21 (! A, c)—as realized in the glomerular (gynecomastia) in the male, among other
zone of the adrenal cortex—makes the steroid things. For normal estrogen ranges, see table
insensitive to the effects of 17-hydroxylase. As on p. 302.
a result, only mineralocorticoids like corti-
294 costerone and aldosterone (A, d ! e; see also
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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