The first step in hormone action on a target cell is its binding to a specifc hormone receptor. However, recent studies suggest that some hormones are involved in non–receptor-mediated responses. Hormones interact with their receptors exposed on the surface of the target cell or within its cytoplasm or nucleus. In general, two groups of hormone receptors have been identified:  Cell surface receptors interact with peptide hormones or catecholamines that are unable to penetrate the cell membrane. Activation of these receptors as a result of hormone binding rapidly generates large quantities of small intracellular molecules called second messengers. These molecules amplify the signal initiated by hormone–receptor interaction and are produced by activation of membrane-associated G proteins. Examples of such systems include the adenylate cyclase/cyclic adenosine monophosphate (cAMP) system (for most protein hormones and catecholamines), the guanylyl cyclase/cyclic guanosine monophosphate (cGMP) system (an antagonistic system for action of cAMP in some protein hormones), the tyrosine kinase system (for insulin and epidermal growth factor [EGF]), the phosphatidylinositol system (for certain hormones such as oxytocin, gonadotropinreleasing hormone [GnRH], angiotensin II, and neurotransmitters such as epinephrine), and activation of ion channels (as with most neurotransmitters). The majority of second messenger molecules exert a stimulatory function on cell metabolism. Examples of second messenger molecules include cAMP, 1,2-diacylglycerol (DAG), inositol 1,4,5-triphosphate (IP3), and Ca2. An inhibitory response is mainly achieved by cGMP, which interferes with the production of cAMP. The second-messenger molecules produced in the cascade reactions of these systems alter the cell’s metabolism and produce hormone-specific responses (Fig. 21.2).
 Intracellular receptors, which are localized within the cell (mainly within the nucleus), are used by steroids and thyroid hormones that can easily penetrate both plasma and nuclear membranes. Their receptors consist of large multi-protein complexes of chaperones containing three binding domains: a hormone-binding region, a DNA-binding
FIGURE 21.2 • General mechanisms of hormone action. a. This schematic diagram shows the basis for protein hormone action involving cell surface receptors. Hormone molecules bind to the receptor and initiate synthesis of second-messenger molecules. These molecules, in turn, activate a cascade of reactions that produce hormone-specific responses in the stimulated cell. b. This diagram shows the mechanism of action of steroid hormones, which use intracellular receptors. Binding of the hormone to this receptor causes allosteric transformation of the receptor into a form that binds to DNA. This binding leads to mRNA transcription and production of new proteins that produce hormone-specific responses in the stimulated cell.
region, and an amino-terminal region. Binding of the hormone to these receptors causes allosteric transformation of the receptor into a form that binds to chromosomal DNA and activates RNA polymerase activity. This in turn increases transcription of mRNA, resulting in the production of new proteins that regulate cell metabolism. Therefore, hormones acting on intracellular receptors infuence gene expression directly, without the help of a second messenger (see Fig. 21.2).
Regulation of Hormone Secretion and Feedback Mechanism
Regulation of hormonal function is controlled by feedback mechanisms.