Human Physiology, 14th edition (2016)

Endocrine Glands 351

section 13.7). In addition, endothelin-1 is produced by the epithe-

lium of the airways and may be important in the embryological

development and function of the respiratory system.

All paracrine/autocrine regulators control gene expression

in their target cells to some degree. This is very clearly the case

with the various growth factors. These include platelet-derived

growth factor, epidermal growth factor, and the insulin-like

growth factors that stimulate cell division and proliferation of

their target cells. Regulators in the last group interact with the

endocrine system in a number of ways, as will be described in

chapter 19.

Prostaglandins

The most diverse group of paracrine/autocrine regulators is

the prostaglandins. These twenty-carbon-long fatty acids

contain a five-membered carbon ring. Prostaglandins are

members of a family called the eicosanoids (from the Greek

eicosa 5  twenty), which are molecules derived from the pre-

cursor arachidonic acid. Upon stimulation by hormones or

other agents, arachidonic acid is released from phospholip-

ids in the plasma membrane and may then enter one of two

possible metabolic pathways. In one case, arachidonic acid is

converted by the enzyme cyclooxygenase into a prostaglan-

din, which can then be changed by other enzymes into other

prostaglandins. In the other case, arachidonic acid is con-

verted by the enzyme lipoxygenase into leukotrienes, which

are eicosanoids that are closely related to the prostaglandins

( fig.  11.34 ). The leukotrienes are largely responsible for the

symptoms of asthma.

Prostaglandins are produced in almost every organ and

have been implicated in a wide variety of regulatory functions.

The study of prostaglandins can be confusing because of the

diversity of their actions, and because different prostaglandins

may exert antagonistic effects in some tissues. For example, the

smooth muscle of blood vessels relaxes (producing vasodilation)

in response to prostaglandin E 2 (abbreviated PGE 2 ); these effects

promote reddening and heat during an inflammation reaction. In

the smooth muscles of the bronchioles (airways of the lungs),

however, PGF 2 a stimulates contraction, contributing to the symp-

toms of asthma.

The antagonistic effects of prostaglandins on blood clot-

ting make good physiological sense. Blood platelets, which are

required for blood clotting, produce thromboxane A 2. This pros-

taglandin promotes clotting by stimulating platelet aggregation

and vasoconstriction. The endothelial cells of blood vessels, by

contrast, produce a different prostaglandin, known as PGI 2 or

prostacyclin, whose effects are the opposite—it inhibits platelet

aggregation and causes vasodilation. These antagonistic effects

ensure that, while clotting is promoted, the clots will not normally

form on the walls of intact blood vessels (see chapter 13, fig. 13.7).

Examples of Prostaglandin Actions

Some of the regulatory functions proposed for prostaglandins

in different systems of the body are:

1. Immune system. Prostaglandins promote many aspects of

the inflammatory process, including the development of

pain and fever. Drugs that inhibit prostaglandin synthesis

help to alleviate these symptoms.

Figure 11.34 The formation of leukotrienes and

prostaglandins. The actions of these autocrine regulators

(PG  5  prostaglandin; TX  5  thromboxane) are summarized.

Lipoxygenase Cyclooxygenase

Arachidonic acid

PGG 2

PGH 2

COOH

PGI 2

Antiplatelet

aggregation

PGE 2

Smooth muscle

relaxation

PGF 2 α

Smooth muscle

contraction

TXA 2

Leukotrienes

Inflammation

Bronchoconstriction;

vasoconstriction;

capillary permeability Vasodilation Vasodilation Vasoconstriction

Platelet

aggregation

Vasoconstriction

Phospholipids of

plasma membrane