
the: (1) mineralocorticoids, which instruct the renal
tubule to retain sodium; (2) glucocorticoids, which
exert manifold effects on carbohydrate metabolism;
(3) progestins, which are essential for reproduction;
(4) estrogens, which induce female secondary sexual
characteristics; (5) androgens, which induce male
secondary sexual characteristics; and (6) the vita-
min-D hormone, 1,25-dihydroxyvitamin D
3
(1,25-
(OH)
2
D
3
), which is important for regulation of
calcium and phosphorus homeostasis, bone growth,
and development. Also, the bile acids are structurally
related to cholesterol and thus constitute a seventh
member of the steroid family. All of these steroids are
biologically derived from cholesterol.
0005 All steroids are derived from a cyclopentano-
perhydrophenanthrene backbone that comprises
three C
6
cyclohexane rings designated as A, B, and
C, fused to a fourth C
5
cyclopentane ring, notated as
the D ring. Within the family of steroid hormones,
each member is distinguished by chemical alterations
such as isomerization, aromatization, dehydrogen-
ation, and fission in the ring structure, and modifica-
tions such as hydroxylations in the side chains of the
cholesterol backbone that are catalyzed by specific
enzymes present in the endocrine glands. The
chemical formulae of these steroid hormones are
depicted in Figure 1.
Biosynthesis of Steroids
0006 Figure 2 summarizes in general terms the metabolic
pathways leading from cholesterol to the six major
steroid hormones (Table 1). The principal tissues
of synthesis of the five classical steroid hormones
(estrogens, androgens, progestins, glucocorticoids,
and mineralocorticoids) are the adrenal cortex, ovar-
ies, and testes. Also, during pregnancy, the fetal–pla-
cental unit can serve as a source of estrogen and some
other hormones. The sites of synthesis of the sixth
class of steroid hormones, the prohormone vitamin
D
3
and its metabolites, are the skin, liver, and kidney.
The bile acids, which are the seventh important struc-
tural class of mammalian steroids, have no known
hormonal activity; they are principally synthesized
in the liver and are secreted from the gallbladder to
participate in digestion and absorption where they
function as a detergent to solubilize fats.
0007 Figure 3 describes the relationship between the
stimulatory peptide hormone and the six classes of
steroid hormones. The biosynthesis of each steroid
hormone by its endocrine gland is stimulated by a
specific cognate peptide hormone. Thus, for example,
the biosynthesis of cortisol in the adrenal cortex is
only stimulated by its tropic (stimulatory) peptide
hormone adrenocorticotropic hormone (ACTH).
ACTH is only secreted by the anterior pituitary gland.
Biosynthesis of Progestins
0008As evident from Figure 2, the common pathway
leading to the production of six classes of steroid
hormones primarily involves conversion of choles-
terol (which possesses 27 carbon atoms) into pregne-
nolone and then progesterone (which possesses 21
carbon atoms). Progesterone is synthesized by the
corpus luteum of the ovary and placenta and consti-
tutes the chief progestational steroid in humans.
Biosynthesis of Glucocorticoids and
Mineralocorticoids
0009The glucocorticoids and mineralocorticoids are
21-carbon corticosteroids produced by the adrenal
cortex (Figure 1). The principal glucocorticoid in
males is cortisol, while aldosterone is the main
mineralocorticoid.
Biosynthesis of Androgens and Estrogens
0010The androgens, which possess 19 carbon atoms, are
produced in the testes in males, and in the ovaries and
placenta in females. Under some circumstances the
adrenal cortex can also produce physiologically sig-
nificant androgens such as androsterone, 4-andro-
stene-3,17-dione, and dehydroepiandrosterone. The
major naturally occurring steroids with androgenic
activity (in decreasing order of relative potency) are
5a-dihydrotestosterone (5a-DHT; 150–200%), tes-
tosterone (100%), androstanediol (65%), androst-
4-ene-3,17-dione (25%), androsterone (10%), and
dehydroepiandrosterone (10%). The hormonally
active form of testosterone in males is 5a-DHT,
which is chiefly produced in the prostate gland,
although skin, testis, and submaxillary glands also
can produce small quantities.
0011The estrogens, which possess 18 carbon atoms, are
produced in the ovarian follicle, corpus luteum,
and fetal–placental unit. In both males and females,
the adrenal cortex can generate small quantities
of estrone from androst-4-ene-3,17-dione. The
major naturally occurring steroids with estrogenic
activity are estra-3,17b-diol, estra-3,16a,17b-triol,
and estrone.
Biosynthesis of Vitamin D Metabolites
0012Chemically, the vitamin D steroids are secosteroids
because of the breakage of the B-ring, leaving the A-,
C-, and D-rings intact (Figure 1). The parent vitamin
D is produced in the skin from 7-dehydrocholesterol
as a consequence of ultraviolet or sunlight action,
which breaks the 9,10 carbon–carbon bond. The
sites of synthesis of the vitamin D metabolites are the
liver and kidney. The hormonally active forms of vita-
min D are 1,25(OH)
2
D
3
and 24,25-dihydroxyvitamin
HORMONES/Steroid Hormones 3167