C h a p t e r 3 1
Mechanisms of Endocrine Control
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circulation, and are thought to act mainly by paracrine
and autocrine mechanisms. Eicosanoid synthesis often
is stimulated in response to hormones, and they serve as
mediators of hormone action.
An extension of the endocrine system is represented
by numerous cell types with enzymes that modify inac-
tive precursors or less active hormones into highly active
hormones. An example is the conversion of the inactive
circulating plasma protein
angiotensinogen
to highly
active angiotensin II by the enzymatic action of renin,
which is produced by the kidney, and angiotensin-con-
verting enzyme, which is present in the lung (see Chapter
18, Fig. 18-13). Another example is the activation of
vitamin D by two subsequent hydroxylation reactions
in the liver and kidney to produce the highly bioactive
form of vitamin D.
Hormone Synthesis
The mechanisms for hormone synthesis and release
vary with hormone structure. Protein and polypeptide
hormones are synthesized and stored in vesicles in the
cytoplasm of the cell until secretion is required. Other
hormones, such as the lipid-soluble steroid hormones,
are released as they are synthesized.
Vesicle-Mediated Synthesis.
The protein and poly-
peptide hormones comprise the most prominent class
of hormones whose synthesis and release is vesicle
mediated. These hormones are synthesized in the rough
endoplasmic reticulum of the endocrine cell in a manner
similar to the synthesis of other proteins (see Chapter 1).
The appropriate amino acid sequence is dictated by
messenger ribonucleic acids (mRNAs) from the nucleus.
Usually, synthesis involves the production of a precursor
hormone, which is modified by the addition of peptides
or sugar units. These precursor hormones often con-
tain extra peptide units that ensure proper folding of
the molecule and insertion of essential linkages. If extra
amino acids are present, as in insulin, the precursor hor-
mone is called a
prohormone.
After synthesis and sequestration in the endoplasmic
reticulum, the protein and peptide hormones move into
the Golgi complex, where they are packaged in vesicles.
It is in the Golgi complex that prohormones are con-
verted into hormones. Stimulation of the endocrine cell
causes the vesicles to move to the cell membrane and
release their hormones.
The vesicle-mediated pathway is also used for
secretion of a number of nonpolypeptide hormones and
neurotransmitters such as the catecholamines (epineph-
rine and norepinephrine). However, these small mole-
cules do not pass through the full range of intracellular
mechanisms seen in the synthesis and secretion of the
larger protein and polypeptide hormones.
Non–Vesicle-Mediated Synthesis.
Hormones syn-
thesized by non–vesicle-mediated pathways include the
glucocorticoids, androgens, estrogens, and mineralo-
corticoids—all steroids derived from cholesterol. These
hormones are synthesized in the smooth endoplasmic
reticulum, and steroid-secreting cells can be identified
by their large amounts of smooth endoplasmic reticu-
lum. Certain steroids serve as precursors for the pro-
duction of other hormones. In the adrenal cortex, for
example, progesterone and other steroid intermediates
are enzymatically converted into aldosterone, cortisol,
or androgens (see Chapter 32).
The release of hormones synthesized by non–vesicle-
mediated pathways is not fully understood. Historically
it was thought to occur by simple diffusion. In recent
years, however, specific transporters have been impli-
cated in directing some of these classes of hormones
out of the cell. Whether all hormones produced by
non–vesicle-mediated pathways depend on transport-
ers for their secretion remains a subject for further
investigation.
HormoneTransport and Clearance from the
Blood
The signaling of the endocrine system relies on mecha-
nisms that transport blood-borne chemical messengers
to the site of action, and then clear them from the blood
once their action is no longer needed.
Transport Mechanisms.
Hormones that are released
into the bloodstream circulate as either free or unbound
molecules or as hormones attached to transport carri-
ers (Fig. 31-3). Peptide hormones and protein hormones
Endocrine gland (thyroid)
Hormone
Circulation
Distant target cell
Paracrine
Nearby
target cell
Paracrine cell
Autocrine cell
Autocrine
A
B
C
FIGURE 31-2.
Examples of endocrine
(A)
, paracrine
(B)
,
and autocrine
(C)
secretions.
