Endocrine Index Glossary

Overview of Hormone Receptors and Signaling

The first step in a hormone's path toward changing the functioning of a cell is binding of the hormone to its receptor. Receptors are cellular proteins that provide specificity to hormone action. Some hormones find their receptor in virtually all cells of the body (e.g. cortisol), whereas the receptors for other hormones are expressed in only a few cells (e.g. gonadotropin-releasing hormone). One can predict that those hormones with the most broadly distributed receptors will influence a large number of physiologic processes.

Receptors bind hormones with high affinity. Simply put, affinity reflects stability of binding, and a high affinity interaction means that the hormone and receptor bind to each other tightly. Binding affinity can be defined quantitatively by a dissociation constant:

Three components exist in any system containing hormones and their receptors: free hormone (H), free receptor (R) and hormone-receptor complexes (HR). The association of hormone and receptor to form the complex, and the dissociation of the complex back into free hormone and receptor are governed by the law of mass action, with a rate constant for each reaction (referred to here as K1 and K2).

The two rate constants can be combined with the molar concentrations of the free hormone ([H]), unoccupied receptor ([R]), and hormone-receptor complex ([HR]) to define the state of these molecules at equilibrium.

The equation above can be rearranged to define KD - the equilibrium dissociation constant. KD is a measure of affinity: the lower KD is, the higher the affinity of the receptor for the hormone. Another interesting aspect of this relationship is that KD is the concentration of hormone at which one-half of the available receptors are bound to hormone.

Another characteristic of hormone-receptor interactions is that they are saturable. Cells contain a finite number of receptors. As the concentration of hormone molecules increases, the number of hormones bound to receptor will plateau or "saturate" close to the total number of receptors.

Finally, receptors have the property of reversibility. Hormone binds to a receptor, then dissociates without having been altered. This property distinguishes interactions of hormones and receptors from those of enzyme and their substrates.

A given hormone may bind to multiple receptors, and a given receptor may bind multiple hormones. A good example of this is the insulin-like growth factor (IGF) family of hormones. Briefly, IGF-1, IGF-II and insulin are three hormones that each can bind to the other's receptors, but with different affinities. For example, the KD of IGF-I for the IGF-I receptor is 0.2 to 1 nM. Both IGF-II and insulin bind to the IGF-I receptor, but at affinities roughly 1/10th and 1/100-1000th that of IGF-I. IGF-I and IGF-II both bind to the IGF-II receptor, while insulin shows no appreciable binding.

Numerous other examples exist of hormones that bind to multiple receptors and receptors that interact with multiple ligands. Such complexity undoubtedly reflects an evolutionary history of these signalling systems, and helps explain certain aspects of normal and pathologic endocrinology.

It is now time to look in more detail about different families of receptors are coupled to different intracellular signalling mechanisms. Next page please.

Index of: Mechanisms of Hormone Action
Introduction and Index G Protein-Coupled Receptors

Last updated on September 3, 2005
Author: R. Bowen
Send comments via form or email to rbowen@colostate.edu