How Hormones Work

How Hormones Work

Hormones are chemical messengers that relay messages to cells that display specific receptors for each hormone and respond to the signal.

Hormones

A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one cell to another. All multicellular organisms produce hormones; plant hormones are also called phytohormones. Hormones in animals are often transported in the blood.

How Hormones Work

Hormones mediate changes in target cells by binding to specific hormone receptors. In this way, even though hormones circulate throughout the body and come into contact with many different cell types, they only affect cells that possess the necessary receptors. Receptors for a specific hormone may be found on many different cells or may be limited to a small number of specialized cells. For example, thyroid hormones act on many different tissue types, stimulating metabolic activity throughout the body. Cells can have many receptors for the same hormone, but often also possess receptors for different types of hormones. The number of receptors that respond to a hormone determines the cell's sensitivity to that hormone and the resulting cellular response. Additionally, the number of receptors that respond to a hormone can change over time, resulting in increased or decreased cell sensitivity. In up-regulation, the number of receptors increases in response to rising hormone levels, making the cell more sensitive to the hormone, allowing for more cellular activity. When the number of receptors decreases in response to rising hormone levels, called down-regulation, cellular activity is reduced.

Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor protein, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses. Receptor binding alters cellular activity, resulting in an increase or decrease in normal body processes. Depending on the location of the protein receptor on the target cell and the chemical structure of the hormone, hormones can mediate changes directly by binding to intracellular hormone receptors and modulating gene transcription, or indirectly by binding to cell surface receptors and stimulating signaling pathways.

Intracellular Hormone Receptors

Lipid-soluble hormones diffuse across the plasma membrane of cells, binding to receptors inside the cells where they alter gene expression.

Intracellular Hormone Receptors

Lipid-derived (soluble) hormones such as steroid hormones diffuse across the lipid bilayer membranes of the endocrine cell. Once outside the cell, they bind to transport proteins that keep them soluble in the bloodstream. At the target cell, the hormones are released from the carrier protein and diffuse across the lipid bilayer of the plasma membrane of the target cells. They then adhere to intracellular receptors residing in the cytoplasm or in the nucleus. The cell signaling pathways induced by the steroid hormones regulate specific genes within the cell's DNA. The hormones and receptor complex act as transcription regulators by increasing or decreasing the synthesis of mRNA molecules from specific genes. This, in turn, determines the amount of corresponding protein that is synthesized from this RNA; this is known as altering gene expression. This protein can be used either to change the structure of the cell or to produce enzymes that catalyze chemical reactions. In this way, the steroid hormone regulates specific cell processes.

Other lipid-soluble hormones that are not steroid hormones, such as vitamin D and thyroxine, have receptors located in the nucleus. The hormones diffuse across both the plasma membrane and the nuclear envelope, then bind to receptors in the nucleus. The hormone-receptor complex stimulates transcription of specific genes in the same way that steroid hormones do. For example, the active vitamin D metabolite, calcitriol, mediates its biological effects by binding to the vitamin D receptor (VDR), which is principally located in the nuclei of target cells. The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins that are involved in calcium absorption in the intestine. VDR activation in the intestine, bone, kidney, and parathyroid gland cells leads to the maintenance of calcium and phosphorus levels in the blood and to the maintenance of bone content.

Plasma Membrane Hormone Receptors

Hormones that cannot diffuse through the plasma membrane instead bind to receptors on the cell surface, triggering intracellular events.

Plasma Membrane Hormone Receptors

Amino acid-derived hormones and polypeptide hormones are not lipid-derived (lipid-soluble or fat-soluble); therefore, they cannot diffuse through the plasma membrane of cells. Lipid-insoluble hormones bind to receptors on the outer surface of the plasma membrane, via plasma membrane hormone receptors. Unlike steroid hormones, lipid-insoluble hormones do not directly affect the target cell because they cannot enter the cell and act directly on DNA. Binding of these hormones to a cell surface receptor results in activation of a signaling pathway; this triggers intracellular activity to carry out the specific effects associated with the hormone. In this way, nothing passes through the cell membrane; the hormone that binds at the surface remains at the surface of the cell while the intracellular product remains inside the cell. The hormone that initiates the signaling pathway is called a first messenger, which activates a second messenger in the cytoplasm.

One very important second messenger is cyclic adenosine monophosphate (cAMP). When a hormone binds to its membrane receptor, a G protein that is associated with the receptor is activated. G proteins are proteins separate from receptors that are found in the cell membrane. When a hormone is not bound to the receptor, the G protein is inactive and is bound to guanosine diphosphate, or GDP. When a hormone binds to the receptor, the G protein is activated by binding guanosine triphosphate, or GTP, in place of GDP. After binding, GTP is hydrolyzed by the G protein into GDP and becomes inactive.

The activated G protein in turn activates a membrane-bound enzyme called adenylyl cyclase. Adenylyl cyclase catalyzes the conversion of ATP to cAMP. cAMP, in turn, activates a group of proteins called protein kinases, which transfer a phosphate group from ATP to a substrate molecule in a process called phosphorylation. The phosphorylation of a substrate molecule changes its structural orientation, thereby activating it. These activated molecules can then mediate changes in cellular processes.

The effect of a hormone is amplified as the signaling pathway progresses. The binding of a hormone at a single receptor causes the activation of many G-proteins, which activates adenylyl cyclase. Each molecule of adenylyl cyclase then triggers the formation of many molecules of cAMP. Further amplification occurs as protein kinases, once activated by cAMP, can catalyze many reactions. In this way, a small amount of hormone can trigger the formation of a large amount of cellular product. To stop hormone activity, cAMP is deactivated by the cytoplasmic enzyme phosphodiesterase, or PDE. PDE is always present in the cell, breaking down cAMP to control hormone activity; thus, preventing overproduction of cellular products.

The specific response of a cell to a lipid-insoluble hormone depends on the type of receptors that are present on the cell membrane and the substrate molecules present in the cell cytoplasm. Cellular responses to hormone binding of a receptor include altering membrane permeability and metabolic pathways, stimulating synthesis of proteins and enzymes, and activating hormone release.