Endocrine Glands 321be additive or complementary. The action of epinephrine and nor-
epinephrine on the heart is a good example of an additive effect.
Each of these hormones separately produces an increase in cardiac
rate; acting together in the same concentrations, they stimulate an
even greater increase in cardiac rate. The ability of the mammary
glands to produce and secrete milk (in lactation) requires the syn-
ergistic action of many hormones—estrogen, cortisol, prolactin,
and oxytocin—which have complementary actions. That is, each
of these hormones promotes a different aspect of mammary gland
function, so that their cooperative effects are required for lactation.
A hormone is said to have a permissive effect on the action
of a second hormone when it enhances the responsiveness of
a target organ to the second hormone, or when it increases the
activity of the second hormone. Prior exposure of the uterus to
estradiol (the major estrogen), for example, induces the forma-
tion of receptor proteins for progesterone, which improves the
response of the uterus when it is subsequently exposed to pro-
gesterone. Estradiol thus has a permissive effect on the respon-
siveness of the uterus to progesterone.
Vitamin D 3 is a prehormone that must be modified by
enzymes in the kidneys and liver, where two hydroxyl
(OH^2 ) groups are added to form the active hormone
1,25-dihydroxyvitamin D 3. This hormone helps to raise blood
calcium levels. Parathyroid hormone (PTH) has a permissive
effect on the actions of vitamin D 3 because it stimulates the
production of the hydroxylating enzymes in the kidneys and
liver. By this means, an increased secretion of PTH has a per-
missive effect on the ability of vitamin D 3 to stimulate the
intestinal absorption of calcium.Antagonistic Effects
In some situations, the actions of one hormone antagonize the
effects of another. Lactation during pregnancy, for example,
is inhibited because the high concentration of estrogen in the
blood inhibits the secretion and action of prolactin. Another
example of antagonism is the action of insulin and glucagon
(two hormones from the pancreatic islets) on adipose tissue;
the formation of fat is promoted by insulin, whereas glucagon
promotes fat breakdown.Effects of Hormone Concentrations
on Tissue Response
The concentration of hormones in the blood primarily reflects
the rate of secretion by the endocrine glands. Hormones do
not generally accumulate in the blood because they are rapidly
removed by target organs and by the liver. The half-life of a
hormone—the time required for the plasma concentration of a
given amount of the hormone to be reduced by half—ranges
from minutes to hours for most hormones (thyroid hormone,
however, has a half-life of several days). Hormones removed
from the blood by the liver are converted by enzymatic reactions
into less active products. Steroids, for example, are converted
into more water-soluble polar derivatives that are released into
the blood and excreted in the urine and bile.thyroxine that are secreted by endocrine glands but are inactive
until they are converted within their target cells into the active
forms of the hormones.
Common Aspects of Neural
and Endocrine Regulation
The fact that endocrine regulation is chemical in nature might
lead one to believe that it differs fundamentally from neural
control systems that depend on the electrical properties of cells.
However, action potentials (chapter 7) involve the movement of
ions down their electrochemical gradients, and such movements
also accompany the actions of some hormones; thus, changes in
membrane potential are not unique to the nervous system. Also,
most nerve fibers stimulate the cells they innervate through the
release of a chemical neurotransmitter. Neurotransmitters do
not travel in the blood as do hormones; instead, they diffuse
across a narrow synaptic cleft to the membrane of the postsyn-
aptic cell. In other respects, however, the actions of neurotrans-
mitters are very similar to the actions of hormones.
Indeed, many polypeptide hormones, including those secreted
by the pituitary gland and by the digestive tract, have been discov-
ered in the brain. In certain locations in the brain, some of these
compounds are produced and secreted as hormones. In other brain
locations, some of these compounds apparently serve as neu-
rotransmitters. The discovery of polypeptide hormones in unicel-
lular organisms suggests that these regulatory molecules appeared
early in evolution and were incorporated into the function of ner-
vous and endocrine tissue as these systems evolved.
Regardless of whether a particular chemical is acting as
a neurotransmitter or as a hormone, in order for it to function
in physiological regulation: (1) target cells must have specific
receptor proteins that combine with the regulatory molecule;
(2) the combination of the regulatory molecule with its recep-
tor proteins must cause a specific sequence of changes in the
target cells; and (3) there must be a mechanism to turn off the
action of the regulator. This mechanism, which involves rapid
removal and/or chemical inactivation of the regulator mole-
cules, is essential because without an “off-switch” physiologi-
cal control would be impossible.
Hormone Interactions
A given target tissue is usually responsive to a number of dif-
ferent hormones. These hormones may antagonize each other
or work together to produce effects that are additive or comple-
mentary. The responsiveness of a target tissue to a particular
hormone is thus affected not only by the concentration of that
hormone, but also by the effects of other hormones on that tis-
sue. Terms used to describe hormone interactions include syn-
ergistic, permissive, and antagonistic.
Synergistic and Permissive Effects
When two or more hormones work together to produce a particu-
lar result, their effects are said to be synergistic. These effects may