Anatomy and Physiology: How Hormones Work
How Hormones Work
The basic idea of every hormone is that a chemical from one cell can alter the behavior of another cell (except for autocrines, in which the cell alters its own behavior). To understand the basic principle of how this is done, you have to look at the structure of the cell membrane. Those ubiquitous proteins are more than just for transporting materials and for cell recognition. Some of them act as receptors for certain chemicals, such as hormones.
Remember that all cells, except gametes and red blood cells, have a complete complement of DNA, and are thus theoretically able to make all the proteins within their genome (the sum total of all their genes). During development, however, the cells differentiate; certain genes are turned on and others are permanently turned off. As some of those genes produce proteins that act as receptors for certain hormones, the presence of such a protein on a cell membrane makes that cell, and the tissues or organs that are comprised of such cells, targets for those hormones. In this way, hormones that travel throughout the bloodstream may target only a very small part of the body, as in the case of certain hypothalamic hormones acting only on the pituitary, which is no bigger than a pea!
The location of such receptors says a lot about the type of hormone involved. In the case of steroid-based hormones, for example, they are lipid soluble (being lipids themselves), and so they pass right through the cell membrane. The thyroid hormones, as biogenic amines (altered amino acids), are small enough to be able to pass freely through the cell membrane. Once the hormone enters the cell, it travels to the nucleus and binds to the receptor portion of the repressor protein attached to the operator of the operon. By doing so, the repressor becomes inactive and detaches from the operator, allowing mRNA to ultimately transcribe the gene, and a protein is ultimately made. Thus the hormone is directly responsible for the production of that protein, which might in fact be another hormone! Whatever the nature of the protein produced, it will alter the activity either of that cell, or of other cells, thus bringing about the desired response.
Protein-based hormones, on the other hand, cannot pass through the cell membrane, in part because they are not lipid soluble; their action is mainly based on their ability to trigger actions within the cell. These peptides and proteins bind to receptors on specific cells.
As a result of that binding, a number of actions are triggered inside the membrane and the cytoplasm, which, ultimately, cause the programmed effect of the hormone. In this situation the hormone acts as a first messenger, but since it can only act on the plasma membrane, a second messenger is required.
There are a number of steps, but once again, Figure 18.2 will help. After the arrival of the first messenger, a G-protein on the inside of the membrane activates an enzyme called adenylate cyclase to convert ATP (adenosine triphosphate) into cyclic AMP or cAMP (cyclic adenosine monophosphate). cAMP plays the role of the second messenger, which activates protein kinases. These protein kinases, in turn, help to strip a phosphate off of ATP (thus making ADP), and add it to other enzymes; the enzymes are thus phosphorylated. It is the action of these phosphorylated enzymes that results in the hormones' ultimate effect. In some cases a protein kinase may inhibit enzymes, rather than activate, depending on the hormone's action.
Give the Glands a Hand
The release of hormones is the result of several processes that make up the endocrine reflexes. This term makes sense, if you think about it, because these responses really need to function like reflexes; they need to be involuntary. Like reflexes, they function on a stimulus/response system, and the response is always the release of a specific hormone. The stimuli that trigger the response, however, may vary.
In some cases the stimuli may be humoral stimuli, which means that changes in the concentration of ions or molecules in the extracellular fluid (as in parathyroid hormone's release due to extracellular Ca2+ concentration) can cause a response. Neural stimuli refer to the arrival of a neurotransmitter at the junction of a neuron and an endocrine gland (as in the case of the release of epinephrine from the adrenal gland after stimulation from a sympathetic nerve; see The Central and Peripheral Nervous Systems). The last group of stimuli are called hormonal stimuli, in which the arrival of one hormone either stimulates or inhibits the release of another. This is the main means by which the hypothalamus and hypophysis communicate, and by which the hypophysis communicates with other glands.
Despite all these different stimuli, hormones do share a basic tendency to be regulated through negative feedback loops. In this way, hormone levels stay balanced, and the body can maintain homeostasis. Although there are some positive feedback loops, such as the oxytocin (OT) loop with the uterus, they each need to be broken by a specific event, or the release of the hormone would just keep increasing.
With the concepts of the types of hormones, and the way they work, especially the nature of the feedback loops, all that is left is to look at the glands that make up the endocrine system. The pituitary, with its bulb shape on a long stalk called the infundibulum, and its multiple hormones targeting multiple glands, made a great candidate for a master gland, the nickname it held for many years. The protective bone case provided by the sella turcica of the sphenoid bone helped maintain the idea.
Further research, however, established that the release of various regulating hormones controls the hormones of the pituitary. Behind the stalk, there is another gland below the thalamus, hence the name hypothalamus, that really is in charge. Releasing hormones and inhibiting hormones, the products of the hypothalamus, take the title of master gland away from the pituitary.
Excerpted from The Complete Idiot's Guide to Anatomy and Physiology © 2004 by Michael J. Vieira Lazaroff. All rights reserved including the right of reproduction in whole or in part in any form. Used by arrangement with Alpha Books, a member of Penguin Group (USA) Inc.
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