Types of receptors
Transmembrane receptors
Transmembrane receptors are proteins that span the thickness of the plasma membrane of the cell, with one end of the receptor outside (extracellular domain) and one inside (intracellular domain) the cell. When the extracellular domain recognizes the hormone, the whole receptor undergoes a structural shift that affects the intracellular domain, leading to further action. In this case the hormone itself does not pass through the plasma membrane into the cell.
Hormone recognition by transmembrane receptors
The recognition of the chemical structure of a hormone by the hormone receptor uses the same (non-covalent) mechanisms, such as hydrogen bonds, electrostatic forces, hydrophobe and Van der Waals forces. The equivalent between receptor-bound and free hormone equals [H] + [R] <-> [HR], with
[R]=receptor; [H]=free hormone; [HR]=receptor-bound hormone
The important value for the strength of the signal relayed by the receptor is the concentration of the hormone-receptor complex, which is defined by the affinity of the hormone for the receptor, the concentration of the hormone and, of course, the concentration of the receptor. The concentration of the circulating hormone is the key value for the strength of the signal, since the other two values are constant. For fast reaction, the hormone-producing cells can store prehormones, and quickly modify and release them if necessary. Also, the recipient cell can modify the sensitivity of the receptor, for example by phosphorylation; also, the variation of the number of receptors can vary the total signal strength in the recipient cell.
Signal transduction of transmembrane receptors by structural changes
Signal transduction across the plasma membrane is possible only by many components working together. First, the receptor has to recognize the hormone with the extracellular domain, then activate other proteins within the cytosol with its cytoplasmic domain, which the protein does through a shift in conformation. The activated effector proteins usually stay close to the membrane, or are anchored within the membrane by lipid anchorss, a posttranslational modification (see myristoilation, palmitorylation, farnesylation, geranylation, and the glycosyl-phosphatidyl-inositol-anchor). Many membrane-associated proteins can be activated in turn, or come together to form a multi-protein complex that finally sends a signal via a soluble molecule into the cell.
Signal transduction of transmembrane receptors that are ion channels
A ligand-activated ion channel will recognize its ligand, and then undergo a structural change that opens a gap (channel) in the plasma membrane through which ions can pass. These ions will then relay the signal. An example for this mechanism is found in the receiving cell of a synapse.
Signal transduction of transmembrane receptors on change of transmembrane potential
An ion channel can also open when the receptor is activated by a change in cell potential, that is, the difference of the electrical charge on both sides of the membrane. If such a change occurs, the ion channel of the receptor will open and let ions pass through. In neurons, this mechanism underlies the action potential impulses that travel along nerves.
Nuclear receptors
Nuclear (or cytoplasmic) receptors are soluble proteins localized within the cytoplasm or the nucleoplasm. The hormone has to pass through the plasma membrane, usually by passive diffusion, to reach the receptor and initiate the signal cascade. The nuclear receptors are ligand-activated transcription activators; on binding with the ligand (the hormone), they will pass through the nuclear membrane into the nucleus and enable the production of a certain gene and, thus, the production of a protein.
The typical ligands for nuclear receptors are lipophilic hormones, with steroid hormones (for example, testosterone, progesterone and cortisol) and derivatives of vitamin A and D among them. These hormones play a key role in the regulation of metabolism, organ function, developmental processes and cell differentiation. The key value for the signal strength is the hormone concentration, which is regulated by :
- Biosynthesis and secretion of hormones in the endocrine tissue. As an example, the hypothalamus receives information, both electrical and chemical. It produces releasing factors that affect the hypophysis and make it produce glandotrope hormones which, in turn, activate endocrine organs so that they finally produce hormones for the target tissues. This hierarchical system allows for the amplification of the original signal that reached the hypothalamus. The released hormones dampen the production of these hormones by feedback inhibition to avoid overproduction.
- Availability of the hormone in the cytosol. Several hormones can be converted into a storage form by the target cell for later use. This reduces the amount of available hormone.
- Modification of the hormone in the target tissue. Some hormones can be modified by the target cell so they no longer trigger the hormone receptor (or at least, not the same one), effectively reducing the amount of available hormone.
The nuclear receptors that were activated by the hormones attach at the DNA at receptor-specific Hormone Responsive Elements (HREs), DNA sequences that are located in the 
