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Endocrinology
PRINCIPLES OF ENDOCRINOLOGY
John Morris
Introductory guide to endocrinology
Endocrinology is the study of the endocrine system. The endocrine system is one of the major
control systems that use chemical messengers (the other is the nervous system).
Much of our understanding of the normal function of the endocrine system has come from clinical
studies of the effects of excess or deficit of the activity of endocrine systems.
The overall aim of the endocrine course is to help you gain a basic scientific understanding of the
various endocrine systems. Specific objectives will be highlighted in individual lectures and
practicals.
Definitions
Hormone: a chemical messenger released from an endocrine cell to influence the activity of
another/the same cell via a receptor. Hormones are normally present in very low concentrations (10-7
- 10-13 M) in the blood/extracellular fluid. Their receptors are also controlled to determine sensitivity.
Endocrine gland: a well-defined collection of endocrine cells.
Diffuse endocrine systems: many hormone-producing cells not aggregated in glands, but dispersed
(e.g. in the gut).
Neuroendocrine systems: neurons releasing hormones both into the blood stream and in the CNS.
Classical endocrine action is when a chemical messenger (the hormone) released by a cell is
transported via the blood stream to its target cell. This is now much too narrow a concept because
hormones also act via various other routes. These are:
 neuroendocrine – the hormone is released from a neuron into the blood stream.
 paracrine – the hormone acts on local cells via the extracellular fluid.
 autocrine – the hormone acts on the cell producing the hormone.
Functions of the endocrine system
The endocrine system promotes survival of the species by:
(a) promoting survival of the individual.
 Effects on development, growth and differentiation.
 Help in preservation of a stable internal environment - homeostasis (but N.B. this is often
disturbed short-term for long-term gain).
 Responds to an altered external environment - especially emergency ‘stress responses’.
(b) control of the processes involved in reproduction.
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Effects
Hormones can affect any mechanism(s) within target cells. The effects can be divided into those that are:
 Activational - effects that disappear when the hormone is removed.
 Organisational - effects that cause a permanent change in the behaviour of their target cells.
The effects can be very rapid (seconds), intermediate, or prolonged (hours, days).
Controls on the release, synthesis and storage of hormones
 Inputs: can be direct or indirect.
 Central integration: The central nervous system (CNS) integrates endocrine control via the
pituitary gland (see Pituitary lecture) and peripheral endocrine systems.
 Output: the release of defined amounts of hormone in a certain temporal pattern allows both
amplitude and frequency modulation.
 Feed-forward control: e.g. from hypothalamus to pituitary to endocrine organ to target organ.
 Feed-back control (usually negative) by either hormones or their effects - a homeostatic
mechanism. This implies a certain “normal level” of hormone in plasma when ‘at rest’.
Chemical classes of hormones
The chemical nature of a hormone profoundly effects many aspects of its production and action.
Hydrophobic:
Steroids (cholesterol derivatives): steroids e.g. testosterone, progesterone
Prostanoids (arachidonic acid derivatives): e.g. prostaglandins, leukotrienes, thromboxanes
Hydrophilic:
Peptide, polypeptide, protein, glycoprotein e.g. insulin, growth hormone
Bioactive amines e.g. adrenaline, noradrenaline, dopamine
Thyroid hormones (iodothyronines) e.g. thyroxine
Gases e.g. NO (nitric oxide)
Note the very large range of size of the molecules: amines, thyroid hormones, steroids and some
peptides are very small; many polypeptide, protein and glycoprotein hormones are very large.
Biosynthesis of hormones synthesized and stored in endocrine glands
Proteins /peptides/glycopeptides are translated on the rough endoplasmic reticulum and secreted by
either the regulated pathway (e.g. insulin, prolactin) or the constitutive pathway (cytokines, growth
factors). The original translation product (the prohormone) is usually processed proteolytically to
yield the active hormone(s).Many endocrine cells produce more than one active peptide hormone, in
varying amounts. These may be derived: (a) from the same prohormone or (b) from different
prohormones.
Steroids are synthesized rapidly on demand from cholesterol via enzymes in the mitochondria and
smooth endoplasmic reticulum (see Adrenal gland lecture).
Bioactive amines are produced from tyrosine via intracellular enzymes (see Adrenal lecture).
Thyroid hormones (iodothyronines) are produced by iodination and coupling of tyrosyl residues in a
protein (thyroglobulin) which are then released by proteolysis (see Thyroid lecture).
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Hormones produced enzymatically as they are needed by other cells
Angiotensin II is produced by conversion of plasma angiotensin I by angiotensin-converting enzyme
in the lung.
NO is produced from arginine by the intracellular enzyme nitric oxide synthase
Prostanoids are synthesized rapidly on demand from arachidonic acid via the intracellular cyclooxygenase enzymes
Storage of different chemical classes of hormone
Endocrine cells store very different amounts of active hormone.
 Amines and many peptides are stored in large amounts in intracellular vesicles (granules).
Some peptides e.g. growth factors and cytokines are not stored but released as they are made.
 Steroids, prostanoids, gases are not stored to any significant extent.
 Large amounts of iodinated thyroglobulin, the precursor for thyroid hormone synthesis, but not
the free hormone, are stored in the thyroid follicles. However the blood contains a large
reservoir of protein-bound thyroid hormone.
Release of hormones; concentrations in the plasma
The small hydrophobic steroids, prostanoids, thyroid hormones and gases are usually thought to
diffuse through the plasma membrane to reach intracellular targets (However, there is increasing
evidence of transport mechanisms for steroids and thyroid hormones).
Peptides and amines are released by the exocytosis of their secretory granules.
Protein and polypeptide hormones are present typically at nanomolar concentrations in plasma; steroid
hormones at sub-micromolar concentrations, mostly bound to specific proteins.
Transport of hormones in blood and extracellular fluid; ‘half-life’ of hormones
 Free hormone: hydrophilic peptide/protein and amine hormones can circulate freely in
plasma.
 Bound + Free: most steroid and thyroid hormones are substantially bound to specific binding
proteins in the plasma so there is an equilibrium between bound and free.
 Binding of hormones to proteins in the plasma substantially reduces their clearance and thus
extends their ‘half-life’.
Metabolism and excretion of hormones
 Hormones have a variable half-life, but most are deactivated rapidly. The first step in their
metabolism generally destroys their activity.
 Hormones that are internalized with their receptor are usually degraded in the lysosomes of the
target cells.
 Steroid hormones are degraded in the liver (and in target tissues).
 Hormones are also lost by excretion: through the kidneys (water soluble), liver and bile.
Measurement of hormones in blood and tissues
 In both clinical practice and scientific investigation it is essential to be able to measure the
concentration of hormones in body fluids and in endocrine tissues.
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 There are "normal ranges" of plasma concentration. The concentration of hormones can vary
substantially in a normal individual: secretion is in pulses with various rhythms of secretion diurnal, reproductive, seasonal. The variation in plasma levels may have to be taken into
account when determining when to take a sample from a patient.
 Most hormones are now measured by some form of binding assay: most common is the
radioimmunoassay. (These must however be validated by a bioassay to ensure they measure
active hormone).
Endocrine pathology
Any control system can go wrong; endocrine disease is a common cause of severe illness.
 The defect can involve too high or too low:
production of the hormone
release of the hormone
response to the hormone
 The defect may be caused by genetic factors, tumours or autoimmune disease.
 For a particular hormone you will need to know the effects of:
too high or too low plasma levels;
the effects of receptor defects: inactive receptors (hormone resistance
syndromes); constitutively receptors.
Any questions: email john.morris@dpag.ox.ac.uk
Specific core learning objectives: to be able to
* define what is meant by a hormone and an endocrine gland;
* give an account of the different routes whereby hormones affect their targets;
* acquire the transferable skill of understanding general principles to apply to all hormone systems:
* different chemical/physical classes of hormones
* biosynthesis, storage, release and transport of the different classes of hormones
* types of actions of hormones
* feed-forward and feed-back controls on secretion
* give an account of the general principles of endocrine pathology (to apply to later specific examples)
Endocrinology Texts
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Endocrinology chapters in any standard physiology textbook; e.g. Boron & Boulpaep
Textbook of Endocrine Physiology: Griffin & Ojeda; Oxford (relatively short paperback)
Endocrine Physiology: Porterfield & White; Elsevier/Mosby (short paperback)
The Endocrine System: Hinson et al; Churchill (endocrine case histories)
Basic & Clinical Endocrinology: Greenspa; Lange (comprehensive paperback)
Williams Textbook of Endocrinology: Kronenberg et al; Elsevier (large reference)
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