Second-messenger mechanisms employing G proteins and
intracellular second messengers are a common means by which
amino acid–based hormones interact with their target cells. In the
cyclic AMP system, the hormone binds to a plasma membrane
receptor that couples to a G protein. When the G protein is
activated, it couples to adenylate cyclase, which catalyzes the
synthesis of cyclic AMP from ATP. Cyclic AMP initiates reactions
that activate protein kinases and other enzymes, leading to
cellular responses. ±e PIP
-calcium signaling mechanism,
involving phosphatidyl inositol, is another important second-
messenger system. Other second messengers are cyclic GMP and
Endocrine System; Topic: The Actions of Hormones on Target
Cells, pp. 3–7.
Steroid hormones (and thyroid hormone) enter their target
cells and eﬀect responses by activating DNA, which initiates
messenger RNA formation leading to protein synthesis.
Target Cell Speciﬁcity
±e ability of a target cell to respond to a hormone depends on
the presence of receptors, on its plasma membrane or within the
cell, to which the hormone can bind.
Hormone receptors are dynamic structures. High or low levels of
stimulating hormones can change the number and/or sensitivity
of hormone receptors.
Endocrine organs are ductless, well-vascularized glands that
release hormones directly into the blood or lymph. ±ey are small
and widely separated in the body.
±e purely endocrine organs are the pituitary, thyroid,
parathyroid, adrenal, and pineal glands. ±e hypothalamus is a
neuroendocrine organ. ±e pancreas, gonads, and placenta also
have endocrine tissue.
Local chemical messengers, not generally considered part of the
endocrine system, include autocrines, which act on the cells that
secrete them, and paracrines, which act on a diﬀerent cell type
Endocrine System; Topic: Endocrine System Review, p. 3.
The Chemistry of Hormones
Most hormones are steroids or amino acid based.
Endocrine System; Topic: Biochemistry, Secretion,
and Transport of Hormones, p. 3.
Mechanisms of Hormone Action
Hormones alter cell activity by stimulating or inhibiting
characteristic cellular processes of their target cells.
Cell responses to hormone stimulation may involve changes
in membrane permeability; enzyme synthesis, activation, or
inhibition; secretory activity; and mitosis.
of patients need no injected insulin
after two years. The need for long-term
immunosuppression limits this treatment
to only those diabetics who cannot control
their blood glucose by any other means.
Over 90% of known DM cases are
type 2 diabetes mellitus
, formerly called
non-insulin-dependent diabetes mellitus
). Type 2 diabetics produce insulin,
but their insulin receptors are unable
to respond to it, a phenomenon called
. Type 2 DM grows
increasingly common with age and with
the increasing size of our waistlines.
About 12 million people in the U.S. have
been diagnosed with type 2 diabetes, and
roughly half as many are believed to be
undiagnosed victims. Type 2 diabetics are
at risk for the same complications as type
1 diabetics—heart disease, amputations,
kidney failure, and blindness.
A hereditary predisposition is
particularly striking in this diabetic group.
Mutations in any one of several genes
could lead to insulin resistance. About
25–30% of Americans carry a gene that
predisposes them to type 2 diabetes, with
nonwhites affected to a much greater
extent. If an identical twin has type 2
diabetes mellitus, the probability that
the other twin will have the disease is
Lifestyle factors also play a role:
Type 2 diabetics are almost always
overweight and sedentary. Adipose
tissue of obese people overproduces a
number of signaling chemicals including
tumor necrosis factor alpha
which may alter the enzymatic cascade
triggered by insulin binding. The Diabetes
Prevention Program, a major clinical trial,
showed that weight loss and regular
exercise can lower the risk of type 2
diabetes dramatically, even for people at
In many cases type 2 diabetes can be
managed solely by exercise, weight loss,
and a healthy diet. Some type 2 diabetics
also beneﬁt from oral medications that
lower blood glucose or reduce insulin
resistance. A promising new class of drugs
targets the incretin hormones normally
secreted by the gut, enhancing glucose-
dependent insulin release from pancreatic
beta cells using a normal physiological
pathway. However, most type 2 diabetics
must eventually inject insulin.
While we cannot yet cure diabetes,
biotechnology promises to continue to
improve control of blood glucose levels
and thereby tame the monster that is
A CLOSER LOOK