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Post by fawnmarie on Dec 9, 2003 13:50:46 GMT -5
Endocrinology is the study of chemical communication systems that provide the means to control a huge number of physiologic processes.
The first step in understanding endocrinology is to explore the meaning of such terms as hormone, receptor and target cell, and to obtain an understanding of how chemical communication is controlled.
Two systems control all physiologic processes:
The nervous system exerts point-to-point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast.
The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.
The nervous and endocrine systems often act together to regulate physiology. Indeed, some neurons function as endocrine cells.
Endocrinology is the study of hormones, their receptors and the intracellular signalling pathways they invoke.
Distinct endocrine organs are scattered throughout the body. These are organs that are largely or at least famously devoted to secretion of hormones. In addition to the classical endocrine organs, many other cells in the body secrete hormones.
Myocytes in the atria of the heart and scattered epithelial cells in the stomach and small intestine are examples of what is sometimes called the "diffuse" endocrine system.
If the term hormone is defined broadly to include all secreted chemical messengers, then virtually all cells can be considered part of the endocrine system.
A final introductory comment is warranted. Pursuit of an understanding of endocrinology is complicated by several of its principles:
1. All pathophysiologic events are influenced by the endocrine milieu: There are no cell types, organs or processes that are not influenced - often profoundly - by hormone signaling.
2. All "large" physiologic effects are mediated by multiple hormones acting in concert: Normal growth from birth to adulthood, for example, is surely dependent on growth hormone, but thyroid hormones, insulin-like growth factor-1, glucocorticoids and several other hormones are also critically involved in this process.
3. There are many hormones known and little doubt that others remain to be discovered.
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Post by fawnmarie on Dec 9, 2003 13:53:33 GMT -5
What exactly are hormones and how are they different from "non-hormones"?
Hormones are chemical messengers secreted into blood or extracellular fluid by one cell that affect the functioning of other cells.
Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells.
A target cell responds to a hormone because it bears receptors for the hormone. In other words, a particular cell is a target cell for a hormone if it contains functional receptors for that hormone, and cells which do not have such a receptor cannot be influenced directly by that hormone. Reception of a radio broadcast provides a good analogy. Everyone within range of a transmitter for National Public Radio is exposed to that signal (even if they don't contribute!). However, in order to be a NPR target and thus influenced directly by their broadcasts, you have to have a receiver tuned to that frequency.
Hormone receptors are found either exposed on the surface of the cell or within the cell, depending on the type of hormone. In very basic terms, binding of hormone to receptor triggers a cascade of reactions within the cell that affects function.
A traditional part of the definition of hormones described them as being secreted into blood and affecting cells at distant sites. However, many of the hormones known to act in that manner have been shown to also affect neighboring cells or even have effects on the same cells that secreted the hormone.
Nonetheless, it is useful to be able to describe how the signal is distributed for a particular hormonal pathway, and three actions are defined:
1. Endocrine action: the hormone is distributed in blood and binds to distant target cells.
2. Paracrine action: the hormone acts locally by diffusing from its source to target cells in the neighborhood.
3. Autocrine action: the hormone acts on the same cell that produced it.
Two important terms are used to refer to molecules that bind to the hormone-binding sites of receptors:
1. Agonists are molecules that bind the receptor and induce all the post-receptor events that lead to a biologic effect. In other words, they act like the "normal" hormone, although perhaps more or less potently. Natural hormones are themselves agonists and, in many cases, more than one distinct hormone binds to the same receptor. For a given receptor, different agonists can have dramatically different potencies.
2. Antagonists are molecules that bind the receptor and block binding of the agonist, but fail to trigger intracellular signalling events. Antagonists are like certain types of bureaucrats - they don't themselves perform useful work, but block the activities of those that do have the capacity to contribute. Hormone antagonists are widely used as drugs.
Finally, a comment on the names given hormones and what some have called the tyranny of terminology. Hormones are inevitably named shortly after their discovery, when understanding is necessarily rudimentary. They are often named for the first physiologic effect observed or for their major site of synthesis. As knowledge and understanding of the hormone grow, the original name often appears inappropriate or too restrictive, but it has become entrenched in the literature and is rarely changed. In other situations, a single hormone will be referred to by more than one name. The problem is that the names given to hormones often end up being either confusing or misleading. The solution is to view names as identifiers rather than strict guidelines to source or function.
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Post by fawnmarie on Dec 9, 2003 14:08:19 GMT -5
Nature uses a diverse spectrum of molecules as hormones, and knowing the basic structure of a hormone imparts considerable knowledge about its receptor and mechanism of action. Additionally, the simpler structures can often be exploited to generate similar molecules - agonists and antagonists - that are therapeutically valuable.
Like all molecules, hormones are synthesized, exist in a biologically active state for a time, and then degrade or are destroyed. Again, having an appreciation for the "halflife" and mode of elimination of a hormone aids in understanding its role in physiology and is critical when using hormones as drugs.
Most commonly, hormones are categorized into four structural groups, with members of each group having many properties in common:
· Peptides and proteins
· Steroids
· Amino acid derivatives
· Fatty acid derivatives - Eicosanoids
Peptides and Proteins
Peptide and protein hormones are, of course, products of translation. They vary considerably in size and post-translational modifications, ranging from peptides as short as three amino acids to large, multisubunit glycoproteins.
Many protein hormones are synthesized as prohormones, then proteolytically clipped to generate their mature form. In other cases, the hormone is originally embedded within the sequence of a larger precursor, then released by multiple proteolytic cleavages.
Peptide hormones are synthesized in endoplasmic reticulum, transferred to the Golgi and packaged into secretory vesicles for export. They can be secreted by one of two pathways:
· Regulated secretion: The cell stores hormone in secretory granules and releases them in "bursts" when stimulated. This is the most commonly used pathway and allows cells to secrete a large amount of hormone over a short period of time.
· Constitutive secretion: The cell does not store hormone, but secretes it from secretory vesicles as it is synthesized.
Most peptide hormones circulate unbound to other proteins, but exceptions exist; for example, insulin-like growth factor-1 binds to one of several binding proteins.
In general, the halflife of circulating peptide hormones is only a few minutes.
Steroids
Steroids are lipids and, more specifically, derivatives of cholesterol. Examples include the sex steroids such as testosterone and adrenal steroids such as cortisol.
The first and rate-limiting step in the synthesis of all steroid hormones is conversion of cholesterol to pregnenolone.
Pregnenolone is formed on the inner membrane of mitochondria then shuttled back and forth between mitochondrion and the endoplasmic reticulum for further enzymatic transformations involved in synthesis of derivative steroid hormones.
Newly synthesized steroid hormones are rapidly secreted from the cell, with little if any storage.
Increases in secretion reflect accelerated rates of synthesis. Following secretion, all steroids bind to some extent to plasma proteins. This binding is often low affinity and non-specific (e.g. to albumin), but some steroids are transported by specific binding proteins, which clearly affects their halflife and rate of elimination.
Steroid hormones are typically eliminated by inactivating metabolic transformations and excretion in urine or bile.
Amino Acid Derivatives
There are two groups of hormones derived from the amino acid tyrosine:
· Thyroid hormones are basically a "double" tyrosine with the critical incorporation of 3 or 4 iodine atoms.
· Catecholamines include epinephrine and norepinephrine, which are used as both hormones and neurotransmitters.
The circulating halflife of thyroid hormones is on the order of a few days. They are inactivated primarily by intracellular deiodinases. Catecholamines, on the other hand, are rapidly degraded, with circulating halflives of only a few minutes.
Two other amino acids are used for synthesis of hormones:
· Tryptophan is the precursor to serotonin and the pineal hormone melatonin
· Glutamic acid is converted to histamine
Fatty Acid Derivatives - Eicosanoids
Eicosanoids are a large group of molecules derived from polyunsaturated fatty acids. The principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes and thromboxanes.
Arachadonic acid is the most abundant precursor for these hormones. Stores of arachadonic acid are present in membrane lipids and released through the action of various lipases. The specific eicosanoids synthesized by a cell are dictated by the battery of processing enzymes expressed in that cell. These hormones are rapidly inactivated by being metabolized, and are typically active for only a few seconds.
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