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U N I T 9
Endocrine System
Adrenal Cortical Hormones
More than 30 hormones are produced by the adrenal
cortex. Of these hormones, aldosterone is the principal
mineralocorticoid, cortisol (hydrocortisone) is the major
glucocorticoid, and androgens are the main sex hor-
mones. All of the adrenal cortical hormones have a simi-
lar structure in that all are steroids and are synthesized
from acetate and cholesterol. Each of the steps involved
in the synthesis of the various hormones requires a spe-
cific enzyme (Fig. 32-12B). The secretion of both the
glucocorticoids and adrenal androgens is controlled by
ACTH secreted by the anterior pituitary gland.
Cortisol, aldosterone, and the adrenal androgens are
secreted in an unbound state and bind to plasma proteins
for transport in the circulatory system. Cortisol binds
largely to corticosteroid-binding globulin and to a lesser
extent to albumin. Aldosterone and androgens circulate
mainly bound to albumin. It has been suggested that the
pool of protein-bound hormones may extend the dura-
tion of their action by delaying metabolic clearance.
The main site for metabolism of the adrenal corti-
cal hormones is the liver, where they undergo a number
of metabolic conversions before being conjugated and
made water soluble. They are then eliminated in either
the urine or the bile.
Mineralocorticoid Hormones
The mineralocorticoids play an essential role in regu-
lating potassium and sodium levels and water balance.
They are produced in the zona glomerulosa or the outer
layer of cells of the adrenal cortex. Aldosterone secre-
tion is regulated by the renin-angiotensin mechanism
and by blood levels of potassium. Increased levels of
aldosterone promote sodium retention by the distal
tubules of the kidney while increasing urinary losses of
potassium. The influence of aldosterone on fluid and
electrolyte balance is discussed in Chapter 8.
Glucocorticoid Hormones
The glucocorticoid hormones, mainly cortisol, are syn-
thesized in the zona fasciculata and the zona reticularis
of the adrenal cortex. The blood levels of these hormones
are regulated by negative feedback mechanisms of the
hypothalamic-pituitary-adrenal (HPA) system (Fig.
32-13). Just as other hormones from the hypothalamus
control the release of their target pituitary hormones,
corticotropin-releasing hormone (CRH) controls the
release of ACTH. In turn, ACTH controls the release of
cortisol. Levels of cortisol increase as ACTH levels rise
and decrease as ACTH levels fall. There is considerable
diurnal variation in ACTH levels, which reach their peak
in the early morning (around 6 to 8
am
) and decline as
the day progresses.
26
This appears to be due to rhythmic
activity in the CNS, which causes bursts of CRH secre-
tion and, in turn, ACTH secretion. This diurnal pattern
is reversed in people who work during the night and
sleep during the day. The rhythm also may be changed by
physical and psychological stresses, endogenous depres-
sion, and liver disease or other conditions that affect
cortisol metabolism. One of the earliest signs of Cushing
syndrome, a disorder of glucocorticoid excess, is the loss
of diurnal variation in CRH and ACTH secretion.
40,41
The glucocorticoids perform a necessary function in
response to stress and are essential for survival. When
produced as part of the stress response, these hormones
aid in regulating the metabolic functions of the body
and in controlling the inflammatory response. The
actions of cortisol are summarized in Table 32-2. Many
of the anti-inflammatory actions attributed to cortisol
result from the administration of pharmacologic levels
of the hormone.
By far the best-known metabolic effect of cortisol
and other glucocorticoids is their ability to stimulate
gluconeogenesis (glucose production) by the liver. In
the process, body proteins are broken down and their
amino acids are mobilized and transported to the liver,
where they are used in the production of glucose. In
much the same manner that cortisol promotes amino
acid mobilization from muscle, it promotes mobiliza-
tion of fatty acids from adipose tissue. This increased
mobilization of fats by cortisol converts cell metabo-
lism from the use of glucose for energy to the use of
HO
Pregnenolone
Progesterone
Cholesterol
11-Deoxycorticosterone
Dehydroepiandrosterone
Androstenedione
Cortisol
Corticosterone
Aldosterone
11-Deoxycortisol
Site of enzyme action
21-hydroxylase
11- -hydroxylase
Cortex
Medulla
Zona glomerulosa
Zona fasciculata
Zona reticularis
A
B
17-Hydroxy-
pregnenolone
17-Hydroxy-
progesterone
FIGURE 32-12.
(A)
The adrenal gland, showing the medulla
and the three layers of the cortex.The outer layer of the
cortex (zona glomerulosa) is primarily responsible for
mineralocorticoid production, and the middle layer (zona
fasciculata) and the inner layer (zona reticularis) produce the
glucocorticoids and the adrenal androgens.
(B)
Predominant
biosynthetic pathways of the adrenal cortex. Critical enzymes
in the biosynthetic process include 11-
β
-hydroxylase and
21-hydroxylase. A deficiency in one of these enzymes blocks
the synthesis of hormones dependent on that enzyme and
routes the precursors into alternative pathways.
