Integrated Endocrinology

John Laycock, Karim Meeran

• Publisher: Wiley
• Year: 2012
• ISBN:
  9781118450574
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Human Anatomy & Physiology
• Index: Biological Sciences

This innovative textbook provides a readable, contemporary and fully integrated introduction to endocrine glands, their hormones and how their function relates to homeostasis. It explores the pathology of endocrine disease by relating the underpinning science through a wealth of clinical scenarios and examples. The book integrates basic and clinical aspects for a range of endocrine glands and their hormones and includes a number of specialist chapters that also address areas of intense research and clinical interest including the regulation of salt, appetite and endocrine-immune interactions.

• Provides a fully-integrated, scientific and clinical introduction to endocrinology.
• Includes a wealth of colour illustrations to reinforce key concepts.
• Introduces clinical scenarios and leading questions to engage interest and illustrate the relevance of the underpinning science.
• Includes key references and suggestions for further reading at the end of each chapter.

Written by a highly respected and experienced author team this new textbook will prove invaluable to students needing an original, integrated introduction to the subject across a variety of disciplines including biomedical science, pharmacology, bioengineering and pre-clinical medicine.

Chapter 1

The Molecular Basis of Hormones

Endocrine Glands and Their Hormones

Introduction

In 1849 Claude Bernard postulated that the internal environment of the cells in the body (the milieu intérieur) is constantly regulated. In 1855 he also proposed that substances can be synthesised and secreted internally, within the body, by demonstrating the production and release of glucose from the liver. In these ways, perhaps he can be considered to be the ‘father’ of endocrinology even though we would not nowadays consider glucose to be a hormone.

While there are descriptions clearly relating to what we now know as endocrine glands going back at least 2000–3000 years in various parts of the world, it is interesting to note that endocrine glands were first classified as such only from the early 1900s. Initially, there were certain accepted methodologies which were used to ascertain whether or not tissues and organs had a true endocrine function. For example, since hormones are released into the bloodstream, certainly according to the original definition (see section ‘What is a hormone?’), it is not surprising to find that endocrine glands in general have a very high blood flow per gram of tissue compared to most other organs. When assays were sufficiently developed to estimate, and later to measure, hormone levels in the blood, the concentration of a hormone would be expected to be greater in the venous effluent from an endocrine gland than in its arterial affluent. Nowadays, this general principle can be used to precisely locate the presence of an endocrine tumour.

Furthermore, removal of the endocrine gland being studied would be expected to result in observable changes to some aspect of the body's physiology. For example, one classic observation by Berthold, also in 1849, linking the testes (male sex glands) with a specific feature, was the disappearance of the comb on the head of a cockerel—a male characteristic in this species—when the testes were removed. Indeed, transplantation of the testes to another part of the body with an adequate blood circulation apparently restored the cock's comb. Likewise, the appropriate administration of an extract from the suspected endocrine gland should restore that physiological function, following the gland's removal. Clearly, such determining studies as these were essential in identifying what we can now call the ‘classical’ endocrine glands including the thyroid, the parathyroids, the gonads and the adrenals. However, nowadays we also recognise the much more disparate sources of hormones, from tissues not instinctively considered to have an endocrine function. For instance, the heart, lungs, kidneys and liver are better known for their other better described physiological functions than for the production of hormones, and yet this is undoubtedly one of their roles. Clearly the removal of such an organ would be problematic with regard to determining its endocrine function!

What is an Endocrine Gland (or Tissue)?

An endocrine gland (or tissue) is usually defined as a group of cells which synthesises a chemical that is released into the surrounding medium, essentially into the blood. An endocrine gland is most easily recognised if it consists of cells with clearly identifiable, intracellular secretory machinery allowing for the expulsion of synthesised molecules out of that cell into the surrounding medium (blood). This is in contrast to an exocrine gland, such as a salivary gland or the main part of the pancreas, which secretes molecules into a duct leading to the exterior of the body. Nowadays, we know of various endocrine glands and tissues in the body which do not quite so readily fit the description given here; indeed, many of them are better known for other physiological actions. A general classification of endocrine glands would now have to include the following categories.

‘Classic’ Endocrine Glands

Various clearly defined glands have been identified as having an endocrine function and these can be classified as the ‘classic’ endocrine glands. They include the gonads, the thyroid, the adrenals, the parathyroids, the pancreatic islets of Langerhans and the pituitary. Each of these glands produces one or more different hormones. Only those glands producing amino acid–derived (e.g. amine, polypeptide and protein) hormones would contain secretory granules.

Gastrointestinal Tract

Historically, the term hormone was actually used by two physiologists, William Bayliss and Ernest Starling, in 1909 to describe a molecule (secretin) produced by the gastrointestinal tract. This organ is extremely large with a clearly defined physiological function regarding digestion and absorption, and it is also the source of numerous hormones. While many of these hormones have clear gastrointestinal effects and fall within the domain of gastroenterologists, some of them do have more widespread effects including on the central nervous system (CNS). These hormones are of particular interest to endocrinologists currently trying to determine the mechanisms involved in the regulation of food intake, hunger and appetite (see Chapter 16).

Central Nervous System

While the hypothalamus is a part of the brain with a well-defined endocrine function, releasing molecules from nerve endings either into a specific blood portal system linking it to the anterior pituitary or into the general circulation via the posterior pituitary (see Chapter 2), it is quite possible that other parts of the brain also produce molecules which could be secreted into brain fluids such as the intracerebroventricular (icv) or general brain extravascular fluids. Certainly, the dendritic release of molecules known to be hormones into the icv fluid in the third ventricle has opened up possibilities of communication between different parts of the brain using a fluid distinct from blood. Furthermore, within the brain is a small organ which has a more clearly defined endocrine function, called the pineal gland. It is an interesting gland with an afferent nerve pathway originating from the eyes; in Hinduism and Buddhism it is known as the third (or inner) eye, and is considered to be a symbol of enlightenment. It produces melatonin, a hormone which plays a role in regulating various functions related to the internal circadian ‘clock’, located in the suprachiasmatic nucleus in the hypothalamus. It is released during the night and its production is inhibited by daylight.

Placenta

Another tissue which has highly specific reproductive functions, and which has a major endocrine role, is the placenta. During pregnancy many hormones are produced by this tissue, often in conjunction with the developing fetus, so that the endocrine tissue as a whole is often referred to as the feto-placental unit (see Chapter 9).

Other Endocrine Tissues

More recently, and as mentioned earlier, tissues better known for other physiological functions have been shown to have endocrine roles. They include the liver, the kidneys, the heart, the blood and adipose tissue. Immune (e.g. lymphoid) tissue also produces molecules which have ‘endocrine’ effects on their distant target cells.

The cells of an endocrine gland produce molecules for export into the general circulation as a consequence of the integration of various signals reaching those cells. At any given time, these endocrine cells may receive numerous differing signals, some stimulatory and others inhibitory. The manner in which each endocrine cell integrates these various signals is one area of endocrinology which is just beginning to be unravelled.

What is a Hormone?

A hormone is that molecule produced by a certain cell or cells (the endocrine gland or tissue) which is exported out of the cells and is transported to its target cells by a circulating fluid medium, by definition (but not necessarily) the blood. Hormones influence their target cells to respond in a specific way, normally to the benefit of the organism. It is part of the homeostatic response to an altered environment, whether internal or external. The hormone conveys a message from one part of the body to another, and can therefore be considered as a messenger molecule. The response of the target cell to that first messenger, or hormone, is often produced in response to an intracellular cascade of activated or inhibited molecules which can be considered to be ‘second’ messenger systems.

Molecules or metabolites that are nutrients or excretory products would have to be excluded. For this reason, Claude Bernard's original discovery that the liver releases an internal secretion which is the energy substrate glucose means that it does not actually conform to the definition of an endocrine gland on this basis; this secretory product is not a hormone. However, the liver does produce other molecules which are not simple nutrients or excretory products, but which are true messengers (‘first’ messengers) secreted into the bloodstream which carries them to their distant target tissues. Consequently, it can truly be considered to be an endocrine tissue (see Chapter 3). Likewise, the definition has to exclude those molecules secreted from nerve terminals and which traverse the tiny synaptic gaps between neurones to act as neurotransmitters or neuromodulators. Of course, this does not exclude the possibility that neurones, for instance in the CNS, can be endocrine cells producing true hormones. Indeed, the study of these neurones and their neurosecretions is such a rapidly expanding research area that it is now a well-established entity in its own right, called neuroendocrinology.

It is apparent that, despite the definition given here, it is not always easy to appreciate whether a molecule is a hormone or not. For example, consider the group of molecules called cytokines. These are proteins produced by cells of the immune system which clearly have a communicating function between different cells. They are transported by the blood and can have diffuse effects in the body, including the CNS, and therefore act as hormones. This group of molecules includes the interleukins (IL1-18) and various other ‘factors’ such as the tumour necrosis factors and interferons, all components of the immune system. Not surprisingly, endocrinologists and immunologists show much interest in them.

One way we could establish whether a molecule is a hormone or not, is to determine whether it has specific receptors on its target cells. This would certainly allow us to exclude simple nutrients and excretory products which do not have any as such. Indeed, there are occasions when a gene product leads to the discovery of a new protein, which may be a receptor protein, for instance. Such a molecule is sometimes called an orphan receptor until a ligand (a molecule that binds to a receptor, such as a hormone) for it has been identified.

As indicated earlier, hormones, by definition, are chemicals which are produced by specific cells and released into the bloodstream to exert their effects on distant target cells. However, it is quite likely that they can be released into (or enter) other circulating fluids such as the cerebrospinal fluid, seminal fluid, amniotic fluid and lymph. All these fluids are essentially made up of water containing a variety of solutes and ions, maybe cells and cell fragments. As chemicals, some of the hormones will be hydrop...