Mechanism Of Hormone Action

Mechanism of Hormone Action Endocrinology is the subject dedicated to describing the mechanisms of hormone action. Endocrine communication is a type of cellular communication where one cell releases hormones which travel via the blood stream to have an effect on another cell. Cytokines are peptides that have a role in communication and can communicate via autocrine communication (effects itself), paracrine communication (effects neighbouring cell) or juxtacrine communication ( via desmosomes). The difference between cytokines and hormones however, is that while cytokines are released from many types of cells, hormones are released from specific organs. Endocrine glands will produce and secrete ligand, which will affect a receptor specific to the ligand, which will in turn trigger the release of second messengers, which will cause a particular effect. Hormones are classified chemically, as either amines, for example ephinephrine; polypeptides (FSH), proteins (growth hormones), steroids and steroid like ( cortisol) and thyroid hormones. The former three groups are classified as being hydrophilic hormones: they cannot pass through plasma membrane and are bound to cell surface receptors. Steroids are lipophilic: they can diffuse through the membrane and interact with cytoplasmic or nuclear receptors. Thyroid hormones have characteristics of both. Hydrophobic hormones, being water soluable circulate in blood freely (only rarely are they bound to a binding protein) and therefore will have a short half-life as they are more prone to degradation if they are free. On the other hand, lipophilic, are not soluable in plasma and have to be complexed to binding proteins, and hence have a longer half-life. Another difference is that while lipophilic drugs require multienzymatic steps (some of which are rate limiting) for their synthesis, peptide hormones in particular are synthesised as prohormones which are then cleaved to give the active hormone. Another difference is extra glandular transformation: which is common in lipophilic hormones, but rare in the hydrophilic. In the latter, any transformation results in an inactive enzyme, which is not the case with lipophilic horones. Since hydrophobic hormones have a short half life, there is storage, which is not seen in lipophilic hormones, which have longer half-lives. Signal transduction is the process that transfers the message carried by the hormone inside the cell. It is the receptor that has the full program for the activation of the cell, which is initiated once a hormone binds to a ligand. There are different modes of signal transduction in hydrophilic hormones, one example is G-protein- coupled receptor ( draw picture). Other types include ion channel activation, phosphatodylinositol phosphate pathway, tyrosine kinase activation and DNA binding proteins. In lipophilic hormones, signal transduction is slightly different from the process described above. After being carried to the site of action by plasma binding proteins, these pass through the plasma membrane. They can either bind to a cytoplasmic receptor and then to a nuclear receptor, or to the latter directly.

Here the receptor-hormone complex will bind to DNA, this complex acts as a transcription factor promoting RNA polymerase to produce mRNA. The same hormone can have different effects on different receptors. This multiplication of effects allows for conservation of hormone production by the body. The hormone receptor complex however is also able to modulate target cells, by positive or negative feedback. In some cases, the same hormonereceptor complex can produce positive feedback or negative feedback. For example, oestrogen production, stimulated by FSH causes a negative feedback to the pituitary during ovulation, but a positive feedback loop pre-ovulation. Another example of a negative feedback loop is the inhibition of production of growth hormone by the liver by the pituitary due to insulin growth factor 1, which is stimulated by GH itself. This mechanism acts as a check. Also, the same hormone can have opposing effects o: insulin stimulates glucose uptake by muscle cells while inhibiting glycogen synthesis in the same cell. Receptors not only recognise hormones and are activated by them, they act additionally as reservoir for the hormone, and they regulate hormone concentration. The latter, is done by internalisation of the hormone receptor complex, hence decreasing the hormone concentration (the receptor is recycled). Hormone- receptor complexes also affect receptors by regulating their concentrations by modulation. If receptors do not have large affinity to their hormones, then they can bind to more than one hormone. For example, in increased concentration of growth hormone, which can also bind to the prolactin receptor, the patient may complain of lactation (specificity spill over). Both receptor and hormone are important to signal transduction. Pharmaceutically, hormone analogues are synthesised to be able to bind to certain receptors and increase or decrease their activity.