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).