Because they are transported in the blood, hormones can reach virtually all tissues. Yet the response to a hormone is highly specific, involving only the target cells for that hormone. The ability to respond depends upon the presence on (or in) the target cells of specific receptors for those hormones. The receptors for peptide hormones and catecholamines are proteins located in the plasma membranes of the target cells. In contrast, the receptors for steroid hormones and the thyroid hormones are proteins located mainly inside the target cells. The response of a target cell to a chemical messenger is the final event in a sequence that begins when the messenger binds to specific cell receptors.
Hormones can influence the ability of target cells to respond by regulating hormone receptors. In the context of hormones, up-regulation is an increase in the number of a hormone’s receptors, often resulting from a prolonged exposure to a low concentration of the hormone. This has the effect of increasing target cell responsiveness to the hormone. Down-regulation is a decrease in receptor number, often from exposure to high concentrations of the hormone. This decreases target cell responsiveness to the hormone, thus preventing overstimulation. Hormones can down-regulate or up-regulate not only their own receptors but the receptors for other hormones as well. If one hormone induces a loss of a second hormone’s receptors, the result will be a reduction of the second hormone’s effectiveness. On the other hand, a hormone may induce an increase in the number of receptors for a second hormone. In this case the effectiveness of the second hormone is increased.
This latter phenomenon, in some cases, underlies the important hormone-hormone interaction known as permissiveness. In general terms, permissiveness means that hormone A must be present for the full strength of hormone B’s effect. A low concentration of hormone A is usually all that is needed for this permissive effect, which is due to A’s ability to upregulate B’s receptors. For example, epinephrine causes a large release of fatty acids from adipose tissue, but only in the presence of permissive amounts of thyroid hormone. The major reason is that thyroid hormone stimulates the synthesis of receptors for epinephrine in adipose tissue; thus, the tissue becomes much more sensitive to epinephrine. It should be noted, however, that receptor up-regulation does not explain all cases of permissiveness; often the explanation is not known.