Hormones are chemical messengers produced by a variety of specialized secretory cells. They may be transported to a distant site of action (the classical ‘endocrine’ effect) or may act directly upon nearby cells (‘paracrine’ activity). In the hypothalamus, elsewhere in the brain and in the gastrointestinal tract there are many such cells secreting hormones, some of which have true endocrine or paracrine activity, while others behave more like neurotransmitters. The distinction between neurotransmitters that act across synaptic clefts, intercellular factors acting across gap junctions and classical endocrine and paracrine activity is becoming increasingly blurred. There are also many chemical messengers involved in cell regulation such as cytokines, growth factors and interleukins.
Synthesis. storage and release of hormones
Hormones may be of several chemical structures: polypeptide, glycoprotein, steroid or amine. In the case of polypeptides, neural or endocrine stimulation of the specific mRNA increases the synthesis of its hormone product. This is often in the form of a precursor molecule that may itself be biologically inactive. This ‘prohorrnone’ may be further processed before being packaged into granules, in the Golgi apparatus. These granules are then transported to the plasma membrane before release. This release may be in a brief spurt caused by the sudden stimulation of granules often induced by an intracellular Ca2+ -dependent process, or it may be ‘constitutive’ (immediate and continuous secretion).
Most hormones are secreted into the systemic circulation but, in the hypothalamus, they are released into the pituitary portal system. Much higher concentrations of the releasing factors thus reach the pituitary than occur in the systemic circulation.
Many hormones are bound to proteins within the circulation. Only the free (unbound) hormone is available to the tissues and thus biologically active. The binding serves to buffer against very rapid changes in plasma levels of the hormone. This principle is important in interpreting many tests of endocrine function, which often measure total rather than free hormone since binding proteins are frequently altered in disease states. Binding proteins comprise both specific, high-affinity proteins of limited capacity, such as thyroxine-binding globulin (TBG) and other less-specific low-affinity ones, such as prealbumin and albumin. The most important and clinically relevant binding proteins.