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Hormones and receptors: fundamental considerations 

Hormones and receptors: fundamental considerations
Chapter:
Hormones and receptors: fundamental considerations
Author(s):

John W. Funder

DOI:
10.1093/med/9780199235292.003.1022
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date: 19 October 2017

The original endocrine physiologists viewed hormones as responses to homoeostatic challenge, any signal a call to arms; the word is thus derived from the classical Greek ωρμαειν—‘to arouse’. In the twenty-first century a hormone is a molecule—small or large, protein or lipid—secreted in a regulated fashion from one organ and acting on another. The definition is firmly based on the anatomy of the seventeenth century, the histology of the nineteenth, and the physiology of the twentieth. It has been shaped by convention and clinical specialization: gut hormones are the marches between endocrinology and gastroenterology, and the adrenal medulla the territory of the cardiovascular physician. It has been refined by concepts of paracrine—where the secretion of one cell type in a tissue acts on another cell type in the same tissue—and autocrine, where a particular cell type both secretes and responds to a particular signal. Inherent in the concepts of paracrine and autocrine are that the signal is not secreted into blood or lymph, to be distributed more or less throughout the body, but is made locally to act locally. A very good example of a signalling system with both paracrine and autocrine activities is the neuronal synapse.

Inherent in the concept of the signal is that of a receptor: a signal without a receptor is the sound of one hand clapping. Inherent in the concept of a receptor are two functions: that of being able to discriminate between different signals, and to propagate the signal by activating cell membrane or intracellular signal transduction pathways. Discrimination by a receptor between different circulating potential signals is, in the first instance, a function of the likelihood of a particular signal being able to interact with the receptor, for a period of time sufficient to alter the confirmation of the receptor and thus to trigger propagation. This interaction is commonly referred to as binding, and thus the circulating hormone as a ligand (that which is bound). If the structures of ligand and receptors are such that the initial interaction is followed by formation of strong intermolecular bonds between the two, lessening the possibility of dissociation and the receptor returning to an unliganded state, the receptor is said to have high affinity for the ligand (and vice versa). If the binding is followed by propagation of the ‘appropriate’ signal the ligand is classified as an agonist, or active hormone; if a molecule occupies the binding site on the receptor but does not so alter its structure as to propagate a signal, it is classified as a hormone antagonist (and often, by extension, a receptor antagonist). In the past couple of decades, the concepts of ‘agonist’ and ‘antagonist’ have needed to be refined, as noted subsequently in this chapter.

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