Mechanisms of hormone action

The binding of a hormone to its receptor initiates intracellular events that direct the hormone's action. Ultimately, all hormones produce their effects by altering intracellular protein activity. However, the mechanism by which this occurs depends on the location of the hormone receptor. Receptors are typically located on the cell surface or in the cell nucleus. As a result, most hormones carry out their effects by means of two general mechanisms:

• Signal transduction and second messenger systems

• Gene activation

Protein/peptide hormones and the catecholamines are water-soluble substances and, accordingly, are unable to cross the plasma membrane to enter the cell. Therefore, these hormones must bind to their specific receptors on the cell surface. This receptor binding causes a response within the cell by way of signal transduction or by the production of intracellular second messenger molecules. The original, extracellular hormone is considered the first messenger because it carried the signal to the target tissue.

The most common second messenger activated by protein/peptide hormones and catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 10.1. The process begins when the hormone binds to its receptor. These receptors are quite large and span the plasma membrane. On the cytoplasmic surface of the membrane, the receptor is associated with a G protein that serves as the transducer molecule. In other words, the G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. These proteins are referred to as G proteins because they bind with guanosine nucleotides. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone

Hormone , (1st messenger) (

Activation of protein kinases

Phosphorylation of enzymes

Activation of protein kinases

Phosphorylation of enzymes

Altered enzyme activity

Change in cellular metabolism

Figure 10.1 The cyclic AMP second messenger system. The most common second messenger system activated by the protein/peptide hormones and the catechola-mines involves the formation of cAMP. This multistep process is initiated by binding of the hormone (the first messenger) to its receptor on the cell surface. The subsequent increase in the formation of cAMP (the second messenger) leads to the alteration of enzyme activity within the cell. A change in the activity of these enzymes alters cellular metabolism.

binds to its G protein-associated receptor, the G protein releases GDP and binds with guanosine triphosphate (GTP) taken up from the cytoplasm. Upon binding with the GTP, the now activated G protein loses its affinity for the receptor and increases its affinity for the plasma membrane-embedded enzyme, adenylyl cyclase. In turn, the adenylyl cyclase becomes activated and splits adenosine triphosphate (ATP) to form cAMP.

The cAMP molecule serves as the second messenger, which carries out the effects of the hormone inside the cell. The primary function of cAMP is to activate protein kinase A. This kinase then attaches phosphate groups to specific enzymatic proteins in the cytoplasm. The phosphorylation of these enzymes enhances or inhibits their activity, resulting in the enhancement or inhibition of specific cellular reactions and processes. Either way, cellular metabolism has been altered. Several noteworthy aspects of this mechanism of hormonal action include:

• Onset of hormonal effects

• Multiple systems

• Cellular specificity

• Amplification of effect

• Prolonged action of hormones

The onset of the response of cells to the activation of second messenger systems is comparatively rapid (within minutes). This mechanism involves changing the activity of existing enzymes rather than production of new enzymes, which is a more lengthy process. There are many signal transduction and second messenger pathways. For example, another signal transduction system involves the opening and closing of ion channels. Furthermore, some tissues use calcium as a second messenger and others use cyclic guanosine monophosphate (cGMP) or inositol triphosphate (IP3). The cellular specificity of a hormone's effect depends on the different kinds of enzyme activity that are ultimately modified in different target tissues. For example, antidiuretic hormone causes reabsorption of water from the kidneys and constriction of smooth muscle in blood vessels: two very different effects in two very different tissues caused by one hormone. Effects elicited by second messenger systems involve a multistep process. This is advantageous because at many of these steps a multiplying or cascading effect takes place that causes amplification of the initial signal. For example, one molecule of the hormone epinephrine binding to its receptor on a hepatocyte may result in the production of 10 million molecules of glucose. Hormone action is prolonged; once an enzyme is activated, the effects are as long lasting as the enzyme and no longer depend upon the presence of the initiating hormone.

Steroid hormones and thyroid hormone carry out their effects by way of gene activation. In contrast to the protein/peptide hormones, which alter existing enzyme activity, these hormones induce the synthesis of new enzymes that then influence cellular metabolism.

Hormones in this category are lipophilic and easily enter the cells of the target tissue by diffusing through the plasma membrane. The hormone continues into the cell nucleus where it binds to its receptor forming a hormone-receptor complex. Hormone receptors are also capable of binding to DNA at specific attachment sites referred to as hormone response elements (HRE). Each of the steroid hormones binds with its receptor and attaches to a different HRE. Binding of the hormone-receptor complex to the DNA activates specific genes within the target cell, resulting in the formation of mRNA molecules. The mRNA then diffuses into the cytoplasm and binds to a ribosome where protein synthesis takes place. These new proteins serve as enzymes that regulate cellular reactions and processes.

As with signal transduction and second messenger systems, the mechanism of gene activation allows for amplification of the hormone's effect.

For example, a single hormone-activated gene induces the formation of many mRNA molecules and each mRNA molecule may be used to synthesize many enzyme molecules. Furthermore, the effects of hormones using this mechanism are prolonged. As long as the newly synthesized enzyme is active, the effect of the initiating hormone persists.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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