Cellular Effects of Peptide Hormones

The receptors for peptide hormones are found in the cell membrane. Peptides cannot freely diffuse through the lipid bilayer of the cell membrane, so their receptors must be in the outer cell membrane to be available to the hor­mones in the extracellular fluid.

When enzymatic activity is increased by a hormone-receptor interaction, the intracellular concentration of the product of the action of that enzyme increases. For example, many peptide hormones activate the enzyme adeny­lyl cyclase, which increases the intracellular production of cyclic AMP (cAMP) by its action on adenosine triphosphate (ATP). The cAMP activates other intracellular enzymes that ulti­mately bring about the characteristic biologic response to the hormone (e.g., cellular secre­tion, cellular contraction, protein synthesis). The term second messenger is a general term for the intracellular compounds, such as cAMP, that function as an intermediate in the sequence of steps leading to the biologic response. Two other common second messengers involved in the cellular response to peptide hormones are diacylglycerol (DAG) and inositol triphos­phate (IP₃). These second messengers are formed by the action of a membrane-bound enzyme, phospholipase C, on phospholipids in the cell membrane.

Ionic calcium (Ca²⁺) concentration in the cytosol is normally lower than that in typical extracellular fluid, but some cells accumulate even higher concentrations of Ca²⁺ within their endoplasmic reticulum. Increases in cytosolic Ca²⁺ concentrations may result from the entry of extracellular Ca²⁺ through membrane chan­nels or by Ca²⁺ diffusing from within the endo­plasmic reticulum into the cytosol through channels within the membrane of the endoplas­mic reticulum.

The increase in Ca²⁺ begins a series of events that ultimately results in changes in intracellu­lar enzymatic activity and a biologic response.

in many cases the biologic response to peptide hormones is rapid and relatively quickly reversed. For example, the action of antidiuretic hormone on cells in the kidney to change their permeability to water can occur within a matter of minutes. such rapid effects are possible because pathways leading to the biologic effects may only require activation of enzymes (pro­teins) that are already in the cell. When the hormone is removed or degraded, the effects are reversed by the inactivation of these enzymes.

in some cases, the biologic response to peptide hormones is longer lasting because the intracellular pathways lead to an increase in DNA transcription and the formation of mes­senger RNA (mRNA). in these cases, the effect is prolonged by the presence of newly synthe­sized intracellular proteins. The general term for agents that directly influence DNA tran­scription is transcription factor. So peptide hormones may bring about changes in tran­scription factors within cells.