Steroids Interact Directly with the Cell Nucleus Through the Formation of a Complex with Its Cytosolic Receptor, Whereas Protein Hormones Need a Messenger Because They Cannot Enter the Cell
The events that follow binding of the hormone and receptor depend on whether a steroid, protein, or peptide hormone is involved. With steroids, the hormone is able to interact within the cell because of its ability to penetrate the lipoprotein plasma membrane (Figure 33-7).
The interaction of receptor and steroid hormone results in activation of the subsequent complex translocation to the nucleus, where it interacts with specific sites on the chromatin. The result is the production of mRNA, which, when translocated to the ribosomes, directs synthesis of proteins that produce the desired biological result.Protein or peptide hormones require an intermediary to act in their behalf because they are not able to penetrate the plasma membrane of the cell; the intermediary substance is known as a second messenger (Figure 33-8). The best- documented second messenger is cAMP, which is produced by the activation of an enzyme, adenyl cyclase, through interaction of the hormone and receptor in the plasma membrane. The activation of adenyl cyclase and the production of cAMP result in the phosphorylation of protein kinases, which are responsible for the biological response. Other second messengers include cytosolic calcium and its associated phosphodiesterase, calmodulin, as well as inositol triphosphate (IP3) and diacylglycerol, both of which are products of phosphatidylinositol metabolism. An important action of IP3 is the stimulation of intracellular calcium release. One important response to diacylglycerol is the activation of phospholipase A and the formation of arachidonic acid, which leads to formation of members of the prostaglandin family of molecules. The biological response to a protein or peptide hormone- receptor interaction is more rapid than that to steroids; preexisting enzymes arc activated, whereas the biological response to steroid requires the synthesis of enzyme protein.
FIGURE 33-7 Subcellular mechanism of action of a lipophilic hormone (H) via an intracellular receptor fR).The H-R complex induces messenger ribonucleic acid (mRNA) synthesis by binding to an acceptor site (A) on the chromatin. (From Hedge GA, Colby HD, Goodman RL: Clinical endocrine physiology, Philadelphia, 1987, Saunders.)
FIGURE 33-8 ■ Subcellular mechanism of action of a hydrophilic hormone (H) via a membrane receptor (R), adenyl cyclase (AC), and cyclic adenosine monophosphate (cAMP). ATP, Adenosine triphosphate; / and C, inhibitory and catalytic subunits of the kinase, respectively; PDE, phosphodiesterase. (From Hedge GA, Colby HD, Goodman RL: Clinical endocrine physiology, Philadelphia, 1987, Saunders.)