Human Physiology, 14th edition (2016)

350 Chapter 11

Thus far in this text, two types of regulatory molecules have
been considered—neurotransmitters in chapter 7 and hormones
in the present chapter. These two classes of regulatory molecules
cannot be defined simply by differences in chemical structure,
because the same molecule (such as norepinephrine) could be
included in both categories; rather, they must be defined by
function. Neurotransmitters are released by axons, travel across
a narrow synaptic cleft, and affect a postsynaptic cell. Hormones
are secreted into the blood by an endocrine gland and, through
transport in the blood, influence the activities of one or more
target organs.
There are yet other classes of regulatory molecules. These
molecules are produced in many different organs and are active
within the organ in which they are produced. These locally act-
ing chemicals that regulate neighboring cells within an organ are
known generally as paracrine regulators, particularly if they
are produced by one cell type and regulate neighboring cells of a
different type. Regulators that act on the same cells and cell type
that produce them may be called autocrine regulators. Some
examples of these regulators are provided in table 11.9.

Examples of Paracrine

and Autocrine Regulation

Many paracrine regulatory molecules are also known as cytokines,
particularly if they regulate different cells of the immune system,
and as growth factors if they promote growth and cell division in
any organ. This distinction is somewhat blurred, however, because
some cytokines may also function as growth factors. Cytokines
produced by adipose tissue are called adipokines, and those pro-
duced by muscle tissue are called myokines. Some of these also
function as hormones when they are secreted into the circulation
and act on distant organs.

Cytokines produced by lymphocytes (the type of white blood

cell involved in specific immunity—see chapter 15) are also

known as lymphokines, and the specific molecules involved are

called interleukins. The terminology can be confusing because

new regulatory molecules, and new functions for previously

named regulatory molecules, are being discovered at a rapid pace.

As described in chapter 15, cytokines secreted by macrophages

(phagocytic cells found in connective tissues) and lymphocytes

stimulate proliferation of specific cells involved in the immune

response. Neurons and neuroglia release neurotrophins, such as

nerve growth factor and others (chapter 7, section 7.1), which

serve as autocrine regulators in the nervous system.

The walls of blood vessels have different tissue layers

(chapter 13, section 13.6), and the endothelial layer produces

several paracrine regulators of the smooth muscle layer. For

example, nitric oxide —which functions as a neurotransmitter

when it is released by axon terminals (chapters 7 and 8)—is also

produced by the endothelium of blood vessels. In this context it

functions as a paracrine regulator when it diffuses to the smooth

muscle layer of the vessels and promotes relaxation, thereby

dilating the vessels. In this action, nitric oxide functions as the

paracrine regulator previously known as endothelium-derived

relaxation factor. Neural and paracrine regulation interact in

this case, because autonomic axons that release acetylcholine

in blood vessels cause dilation by stimulating the synthesis of

nitric oxide in those vessels (see chapter 20, fig. 20.21).

The endothelium of blood vessels also produces other para-

crine regulators. These include the endothelins (specifically endo-

thelin-1 in humans), which directly promote vasoconstriction, and

bradykinin, which promotes vasodilation. These regulatory mol-

ecules are very important in the control of blood flow and blood

pressure. They are also involved in the development of atheroscle-

rosis, the leading cause of heart disease and stroke (chapter 13,

Table 11.9 | Examples of Paracrine and Autocrine Regulators

Paracrine or Autocrine Regulator Major Sites of Production Major Actions

Insulin-like growth factors (somatomedins) Many organs, particularly the liver and cartilages Growth and cell division

Nitric oxide Endothelium of blood vessels; neurons;

macrophages

Dilation of blood vessels; neural

messenger; antibacterial agent

Endothelins Endothelium of blood vessels; other organs Constriction of blood vessels; other effects

Platelet-derived growth factor Platelets; macrophages; vascular smooth muscle

cells

Cell division within blood vessels

Epidermal growth factors Epidermal tissues Cell division in wound healing

Neurotrophins Schwann cells; neurons Regeneration of peripheral nerves

Bradykinin Endothelium of blood vessels Dilation of blood vessels

Interleukins (cytokines) Macrophages; lymphocytes Regulation of immune system

Prostaglandins Many tissues Wide variety (see text)

TNFa (tumor necrosis factor alpha) Macrophages; adipocytes Wide variety