MadSci Network: Biochemistry

Re: How does a hormone go about exerting its effect?

Area: Biochemistry
Posted By: Michael Onken, WashU
Date: Sat Sep 27 17:09:50 1997
Area of science: Biochemistry
ID: 873830113.Bc

Hormones are a widely diverse group of compounds which are used to transmit information from one cell to one or more other cells (or even to itself). For any cell to respond to a given hormone, it must already have a specific receptor for that specific hormone. Receptors are proteins expressed by cells which allow the cells to identify things in their environments, including hormones. From the point of view of the hormone, it simply binds to its receptor which then activates the cell. However, one of the major areas of research going today is signal transduction , which is the mechanism that allows receptor-binding to influence what goes on in the cell. One of the first discoveries was that different receptors use different pathways to affect the cell.

Nuclear Hormone Receptors are receptors that bind fatty (lipophilic) hormones, like steroids, vitamin D, or retinoic acid. Because of their affinity for lipids, the hormones can pass directly through the cells outer membrane and into the cytoplasm. Once in the cell, these hormones bind to receptors, triggering them to form pairs (dimerize) and head directly into the nucleus. In the nucleus, the hormone:receptor complexes bind to specific regions of DNA on the chromosomes, and activate a number of genes that change the way the cell functions. This is the simplest form of hormone signalling, since the receptors are also transcription factors.

G-protein Receptors are receptors that recognize small water soluble hormones, like adrenalin (epinephrine), and a host of neurotransmitters, in fact the chemoreceptors in your nose that allow you to smell are G-protein receptors, as are the photoreceptors in your eyes that allow you to see. These hormones cannot get through the cell membrane like the steroids, so their receptors sit inside the membrane, coiling in and out of the cell seven times (giving them the collective name of 7-Transmembrane-Domain Proteins) and looking like half-closed baseball mitts poking through the membrane. Each receptor is attached to G-proteins on the cytoplasmic face of the membrane. G-proteins get their name from their need for GTP (one of the building blocks of RNA) to be active. When the right hormone binds to a receptor, it alters the shape of the receptor, allowing it to activate any G-proteins it contacts. The G- proteins then diffuse along the face of the membrane and activate specific target proteins, which (directly or indirectly) produce secondary messengers, including cAMP and Ca2+. These secondary messengers can activate many cellular activities, including membrane depolarization, cytoskeleton rearrangement, and gene activation.

Tyrosine Kinase Receptors are receptors that bind to proteinaceous hormones, like insulin and Growth Factors. These hormones are large, soluble proteins that again cannot cross the cell membrane and require a receptor to transmit their signal from the outside of the cell to the cytoplasm. In this case, the receptors only cross the membrane once, giving them a linear orientation with three distinct domains: an extracellular domain which binds the hormone; a transmembrane domain; and a cytoplasmic domain which generates the signal to activate the cell. In this case, binding of hormones causes the extracellular domains of the receptors to dimerize, which in turn brings their cytoplasmic domains close together. Once in contact, the cytoplasmic domains enzymatically add phosphates to each other at the amino acid tyrosine (an enzyme which adds phosphates to other molecules is called a "kinase", so these receptors are "tyrosine kinases"). There are a host of other enzymes in the cell which bind phoshpo-tyrosines (P-Tyr) and are activated when the receptors phosphorylate each other. These P-Tyr binding proteins (many of which are themselves kinases) can then produce secondary messengers or directly activate the fated Ras/MAP Kinase Pathway which sends the signal to the nucleus (among other places) to activate a slew of genes involved in cell growth and proliferation. I should add that some of these receptors have stubby cytoplasmic tails which rely on binding to auxilliary proteins for their kinase and signaling activities.

To pull it all together, hormones exert their affects through binding to receptors which are produced by the target cells. These receptors, then, are responsible for converting the presence of the hormone into a signal the cell can understand. Most importantly, since the receptors are required for hormone activation, only cells expressing the correct receptors can be influenced by a given hormone. Because all cell do not express all hormone receptors, hormones are an easy way for cells in one part of the body to influence cells in another part of the body without affecting the entire organism.

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