All cellular structures and functions are determined by proteins. Structural proteins determine the general shape and internal structure of a cell, and enzymes direct the cell's metabolism. Hormones alter cellular operations by changing the identities, activities, locations, or quantities of important enzymes and structural proteins in various target cells. A target cell's sensitivity is determined by the presence or absence of a specific receptor with which a given hormone interacts. Hormone receptors are located either on the cell membrane or inside the cell.
The receptors for epinephrine, norepinephrine, peptide hormones, and eicosanoids are in the cell membranes of their respective target cells. Because epinephrine, norepinephrine, and the peptide hormones are not lipid soluble, they cannot diffuse through a cell membrane, and they bind to receptor proteins on the outer surface of the cell membrane. Eicosanoids, which are lipid soluble, diffuse across the cell membrane and bind to receptor proteins on the innner surface of the cell membrane.
Hormones that bind to cell membrane receptors do not have direct effects on the target cell. Instead, when these hormones bind to an appropriate receptor, they are considered first messengers that then trigger the appearance of a second messenger in the cytoplasm. The link between the first messenger and the second messenger usually involves a G protein, an enzyme complex that is coupled to a membrane receptor. The G protein is activated when a hormone binds to the hormone's receptor at the membrane surface. The second messenger may function as an enzyme activator or inhibitor, but the net result is a change in the cell's metabolic activities.
One of the most important second messengers is cyclic AMP (cAMP). Its appearance depends on an activated G protein, which activates an enzyme called adenylate cyclase. In turn, adenylate cyclase converts ATP to a ring-shaped molecule of cAMP. Cyclic-AMP activates kinase enzymes, which attach a high-energy phosphate group (PO
43-) to another molecule in a process called phosphorylation.
The effect on the target cells depends on the nature of the proteins affected. The phosphorylation of membrane proteins can open ion channels, and in the cytoplasm many enzymes can be activated only by phosphorylation. As a result, a single hormone can have one effect in one target tissue and quite different effects in other target tissues. The effects of cAMP are usually very short-lived, because another enzyme in the cell, phosphodiesterase (PDE), quickly breaks down cAMP. In a few instances, the activation of a G protein can lower the concentration of cAMP within the cell by stimulating PDE activity. The decline in cAMP has an inhibitory effect on the cell because without phosphorylation key enzymes remain inactive.
Although cyclic-AMP is one of the most common second messengers, there are many others. Important examples are calcium ions and cyclic-GMP, a derivative of the high-energy compound guanosine triphosphate (GTP).
Steroid hormones and thyroid hormones cross the cell membrane before binding to receptors inside the cell. Steroid hormones diffuse rapidly through the lipid portion of the cell membrane and bind to receptors in the cytoplasm or nucleus. The resulting hormone-receptor complex then activates or inactivates specific genes in the nucleus. By this mechanism, steroid hormones can alter the rate of mRNA transcription, thereby changing the structure or function of the cell. The steroid hormone testosterone, for example, stimulates the production of enzymes and proteins in skeletal muscle fibers, increasing muscle size and strength.
Thyroid hormones cross the cell membrane either by diffusion or by a transport mechanism. Once within the cell, thyroid hormones bind to receptors within the nucleus or on mitochondria. The hormone-receptor complexes in the nucleus activate specific genes or change the rate of mRNA transcription. The result is an increase in metabolic activity due to changes in the nature or number of enzymes in the cytoplasm. Thyroid hormones bound to mitochondria increase the mitochondrial rates of ATP production.
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