Mechanisms of steroid hormone activity
Steroid hormones are signalling molecules responsible for communication between cells. This communcation can happen between neighbouring cells in the same organ, or be targeted at distant organs and travel there in the bloodstream. The signals transmitted by steroid hormones have a huge variety of roles, but are often to do with cell growth and proliferation: the regulation of tissue development and each cell’s drive through the cell cycle.
The hormones themselves are based on cholesterol molecules which have been absorbed from the diet and modified. As lipid-based molecules, they are non-polar and can pass in and out of cells.
This distinguishes them from the other main class of signalling molecules: protein and peptide hormones, which are usually polar or charged and can’t get through the phospholipid bilayer membranes that surround cells. They have to bind to receptors on the cell surface, which then communicate their arrival to the interior of the cell. These cell surface receptors are usually enzymatic in nature and have very fast actions, resulting in changes in cell behaviour which can be seen in seconds.
The classical genomic pathway of steroid hormone activity
This is how the acticity of these hormones is usually understood: The steroid hormone is released by a gland or tissue and enters the blood. It circulates around until it reaches its target organ, where it diffuses into the tissue and through the cell membrane of a target cell. Once inside the cytoplasm, it finds a specific receptor for it. The receptor is a protein with a binding site specific for the hormone, a DNA-binding sequence and a protein binding site which is usually occupied by a second large protein complex. The job of this second complex is to ensure the receptor is inactive when the hormone is not present.
Once the hormone binds, the receptor changes shape and releases the large protein complex. The hormone and receptor are now small enough to pass through the nuclear membrane. Once in the nucleus, the protein binding site of the receptor is occupied by a general nuclear receptor. This final complex finds the approtiate section of DNA, binds to it and recruits transcriptional machinery which then ensure the production of protein from the relevant gene. The protein product then changes the behaviour of the cell, which is evident usually a few hours after the hormone was first released.
Non-genomic rapid actions
The first sign that this model could not be the complete picture came in 1963, in a German study of the actions of aldosterone, a steroid hormone involved in the long-term regulation of blood pressure. Alterations in the behaviour of blood vessels were seen just two minutes after the introduction of aldosterone, far too quickly to have been caused by production of protein.
This finding was later compounded by others: Estrogen was found to mediate effects on target tissues even when it was bound to albumin, a huge serum protein which would completely prevent it from crossing the cell membrane. Estrogen surface receptors were identified, and the nearby cytoplasm experienced large rises in cyclic AMP when the hormone was present: a tell-tale sign of an enzymatic signalling pathway inside the cell. Such enzyme pathways are involved in most protein hormone binding. Similar findings have been reported in the other steroid hormones, although data is less extensive.
What is certain is that steroid hormones play a much wider and more varied role in cell signalling than was previously believed. They are not just the drivers of cell growth and tissue development: they can also control rapid responses to external stimuli, a job which had always been credited to the protein hormones.