Hormones regulate metabolic activity in various tissues. They are one kind of mechanism for signaling among cells and tissues. Hormones can be defined as signaling molecules that one cell releases into the peripheral fluid or bloodstream, which alter the metabolism of the same or another cell. Hormones are distinguished from communication mechanisms that depend on direct cell‐cell contact through gap junctions. Hormones are also distinguished from neurotransmitters, although this distinction is somewhat artificial. Neurotransmitters can act as hormones and vice versa.
Hormones act by binding to receptors, which are usually protein molecules. Receptors have two functions: first, they bind the hormone, and secondly, they transduce (change the type of) the signal to affect the metabolism of the recipient cell. The ability of a cell to respond to a hormone depends on two properties of the receptor molecule: how many of them are on a particular cell, and how well they bind the hormone. The first property is called the receptor number, and the second is called the affinity of the receptor for the hormone. The biochemical responsiveness of a cell to a hormone (or a drug, or a neurotransmitter) depends on the number of occupied receptor son the responsive cell. Suppose that a hormone binds to a receptor with a dissociation constant given by the following equation:
In the equation, R is the receptor, H is the hormone, and RH is the hormone‐receptor complex. If 50 occupied receptors trigger the appropriate metabolic response, you can achieve the response by having 100 receptors on a cell with half of them occupied or by having 55 receptors on a cell with 90 percent of them occupied. How can this be achieved? If the second set of receptors had a tenfold greater affinity for the hormone, the same concentration of hormone would result in 50 bound receptors.
Rearranging the previous equation to solve for [H], the level of circulating hormone yields
If two receptors exist, types 1 and 2, each of which is responding to a constant concentration of hormone, [H], then
(Remember that the higher K d means a lower affinity.)
If you set the number of occupied receptors [RH 1] = [RH 2] = 50, you can solve for the number of unoccupied receptors of each type [R 1] = 50, and [R 2] = 5. In other words, one receptor type has a greater occupancy than the other does.
Suppose the hormone concentration increased by 50 percent. In this case, the first receptor system, R 1, would be more responsive. R 2 would be close to saturation; complete saturation of R 2 would yield only five more occupied receptors. This means that the concentration of occupied receptors can change most when the receptor is about half occupied. The previous equations show that the maximum responsiveness to a change in hormone concentration is possible when the association constant of the receptor for a hormone is near the physiological concentration of the hormone.
The compounds that bind to a receptor can modulate the actions of that receptor. Agonists act to reinforce the activity of a receptor by binding to it and mimicking the action of the receptor. Antagonists bind to a receptor but do not cause the action of the receptor. Drugs can be either agonists or antagonists. For example, isoproteranol is an agonist for a receptor that increases blood pressure, while propanolol—a commonly used drug to decrease blood pressure—is an antagonist for another class of receptors. Both of these compounds are structurally related to the natural hormone epinephrine.
When cells are continually occupied, they reduce the number of receptors to avoid having the metabolic effects overstimulated. For example, two kinds of diabetes exist, Type I and Type II. Type I diabetes, sometimes called juvenile diabetes, results from the inability of the pancreas to supply insulin. Type II diabetes, sometimes called adult‐onset diabetes, is more common and correlates with obesity. In this situation, the body senses itself to be in a well‐fed state and releases insulin from the pancreas. The large concentration of insulin causes the recipient cells to be fully stimulated. Consequently, they down‐regulate their insulin receptor population to bring the response into the normal range. Reducing the total number of receptors reduces the number of occupied receptors. Unfortunately, the lower number of occupied receptors means that blood glucose concentrations are not well regulated and can increase to an abnormally high level, leading to the side effects of diabetes, including problems with vision and circulation.
Hormone receptors are of two types. Cell‐surface receptors for water‐soluble hormones lead to a metabolic response. For example, receptors for the small molecule epinephrine and for the peptide growth hormone are of this type. A protein in the cell membrane binds the hormone and then causes the synthesis of a second messenger, which leads to a metabolic response.
Internal or cytoplasmic receptors for lipophilic hormones lead to gene activation. For example, the steroid hormones, including estrogen and adrenal hormones, bind to intracellular receptors. When occupied, these receptors then move to the cell nucleus and affect transcription of specific genes, either positively or negatively. Some hormones—including insulin—exert both metabolic and genetic changes when bound to surface receptors.
Metabolic hormones do not exert their effects directly but rather are transduced into an intracellular signal. Transduction refers to the process by which one kind of signal is converted to another.