Endocrine Control
Multicellular
organisms must coordinate the diverse activities of their cells, often over large distances. In animals,
such coordination is achieved by the nervous and endocrine systems, the
former providing rapid, precise but short-term control and the latter providing
generally slower and more sustained signals. The two systems are intimately
integrated and in some places difficult to differentiate. Endocrine control is
mediated by hormones, signal molecules usually secreted in low
concentrations (10−12–10−7 m) into the bloodstream, so that they can reach all
parts of the body. Other types of chemical communication are mediated over
smaller distances. Chemical signals can act locally on neighbouring cells (paracrine
signals) or can act on the same cell that produced the signal (autocrine
signals); juxtacrine communication requires direct physical contact
between signal chemicals on the surface of one cell and receptor molecules on
the surface of a neighbour. Many hormones are secreted by discrete glands
(Table 42), while others are released from tissues with other primary
functions. For instance, several of the cytokines released by immune cells
(Chapter 10) act at some distance
from their site of release and can fairly be considered as hormones.
Features of hormonal signalling
Hormonal molecules can be: (i) modified
amino acids [e.g. adrenaline (norepinephrine); Chapter 49]; (ii) peptides
(e.g. somatostatin; Chapter 44); (iii) proteins (e.g. insulin;
Chapter 43); or (iv) derivatives of the fatty acid cholesterol, such as steroids
(e.g. cortisol; Chapter 49; Table 42). Protein and peptide hormones are
cleaved from larger gene products, whereas smaller molecules require the
precursor to be transported into endocrine cells so that it can be modified by
sequences of enzymes to generate the final product (e.g. Chapter 49). Most
hormones are stored in intracellular membrane-bound secretory granules,
to be released by a calcium-dependent mechanism similar to the release
of neurotransmitters from nerve cells (Chapter 7; Fig. 43b) when the cell is
activated. However, thyroid hormones and steroids, which are highly lipid
soluble, cannot be stored in this way. Most steroids are made immediately
before release, whereas the thyroid hormones are bound within a glycoprotein
matrix (Chapter 45). After secretion, some hormones bind to plasma proteins.
In most cases this involves non-pecific binding to albumin, but there are specific
binding proteins for some hormones, such as cortisol or testosterone. A
hormone bound to a plasma protein cannot reach its site of action and is
protected from metabolic
degradation, but is freed when the plasma level of the hormone falls. The bound fraction thus acts as
a reservoir that helps to maintain steady plasma levels of the free hormone.
Hormones exert their effects by
interactions with specific receptor proteins and will act only on cells
carrying those receptors. Most protein and peptide hormones activate cell
surface receptors that are coupled to guanosine
triphosphate-binding proteins (G-proteins) (Chapter 4) or that have intrinsic
tyrosine kinase activity (e.g. Chapter 43). Receptors for lipid-soluble
hormones (steroids, thyroid hormones) are usually inside the target
cell, and modify gene transcription directly (e.g. Chapter 45). Because they
are in the bloodstream, free hormones can reach all of the tissues that bear
the appropriate receptors. Endocrine signals therefore provide a good way of
inducing simultaneous changes in multiple organs, and most hormones have
effects in more than one tissue. A corollary of this position is that many
physiological processes are influenced by more than one hormone, as will become
clear in subsequent chapters. Hormones are inactivated by metabolic
transformation by enzymes, usually in the liver or at the site of action. It is
a general rule that the smaller the hormone, the more rapid its inactivation.
Control of hormones
Endocrine secretion can be controlled by the nervous system, other
endocrine glands, or respond directly to levels of metabolites in the
environment of the gland, and most are subject to all of these types of
control. A common feature of hormonal control systems is a heavy reliance on negative
feedback loops. Almost all hormones feed back to inhibit their own release,
providing a direct method of moderating the output of hormone into the blood
(Chapters 44–53). A less common feature of endocrine systems, associated only
with reproductive functions, is positive feedback, whereby the
release of a hormone leads to events that further promote release (Chapters 50,
51 and 53). The carriage of hormones in the blood provides a limit on how
quickly hormones produce their effects. The relatively slow nature of hormonal
signalling puts limits on the types of physiological processes that can be
controlled by hormones. They fall into four broad categories: (i) homeostasis;
(ii) reproduction; (iii) growth and development; and (iv) metabolism. These systems work over
time-scales that range from a few minutes
(e.g. milk ejection;
Chapter 53) to
years (growth; Chapter 47).
