Steroids and Athletes: Genes Work Overtime 0/8
How Does an Anabolic Steroid Reach its Target?
Once in the bloodstream, the anabolic steroid travels to all tissues in the body, where it enters the cells to reach its target. In order to get into a muscle cell for example, the steroid must leave the capillary and then enter the muscle cell. This means that the steroid must cross two different types of membranes, the capillary membrane and the muscle cell membrane. To cross the capillary membrane, there are numerous pores or fenestra1, which allow small molecules to squeeze through (Figure 3 and see Module 1). However the muscle cell membrane (like most cells in the body) does not have these small pores and therefore the steroid can only cross the membrane by diffusing across or by transport via a carrier protein. Steroids cross the cell membrane by passive diffusion2, which occurs in the direction of the concentration gradient – this does not require energy. Passive diffusion depends on the physiochemical characteristics of the membrane and the drug3. The muscle cell membrane, like all cell membranes in the body, is a lipid bilayer (Figure 4). It consists of lipids arranged with their polar4 head groups facing the outside and inside of the cell. The chains of fatty acids face each other, forming the hydrophobic5(water-fearing) or non-polar6 interior. Because anabolic steroids7 are very lipophilic8 (lipid-loving), they diffuse easily into the hydrophobic membrane interior. As they concentrate within the hydrophobic membrane interior, a new driving force is generated, pushing the steroid into the cytoplasmic side of the cell membrane. Once the anabolic steroid diffuses into the cytoplasm of the cell, it binds to the androgen receptor9 (Figure 5). [Receptors for other steroids are found in the nucleus instead of the cytoplasm.] This complex of steroid and protein then crosses the nuclear membrane to enter the nucleus of the cell, where it exerts its effects. In this case, passive diffusion can’t occur because the protein is too large and not lipophilic. Instead, the steroid-receptor complex moves through small pores in the nuclear membrane to enter the nucleus. Although scientists are still elucidating exactly how this occurs, it is possible that the complex interacts with transport proteins that line the nuclear pores. This is an example of facilitated diffusion10, which occurs in the direction of the concentration gradient. Therefore, no energy is required. This is unlike active transport11, which occurs against the concentration gradient, and requires energy.
1 small spaces or pores within endothelial cells that form the capillary membrane. These pores allow charged drugs or larger drugs to pass through the capillaries.
2 the movement of a solute in its uncharged form to cross a membrane along a concentration gradient. No energy is required.
3 a substance that affects the structure or function of a cell or organism.
4 a chemical property of a substance that indicates an uneven distribution of charge within the molecule. A polar substance or drug mixes well with water but not with organic solvents and lipids. Polar or charged compounds do not cross cell membranes (lipid) very easily.
5 “water-fearing”; a compound that is soluble in fat but not water. This is typical of compounds with chains of C atoms.
6 a chemical property of a substance that indicates an even distribution of charge within the molecule. A non-polar or non-charged compound mixes well with organic solvents and lipids but not with water.
7 synthetic versions of testosterone designed to promote muscle growth without producing androgenic effects. The better term is anabolic-androgenic steroid.
8 high lipid solubility. Lipophilic compounds dissolve readily in oil or organic solvent. They exist in an uncharged or non-polar form and cross biological membranes very easily.
9 a protein to which hormones, neurotransmitters and drugs bind. They are usually located on cell membranes and elicit a function once bound.
10 the movement of molecules across a membrane with the concentration gradient. No energy is required, but transport proteins can become saturated, limiting the diffusion process.
11 the movement of molecules against the concentration gradient with the help of a transport protein. This transport requires energy in the form of ATP.
Figure 4 Schematic view of cell membrane. Lipids are arranged with polar head-groups facing the outside and inside of the cell, while the fatty acid chains form the non-polar (hydrophobic) membrane interior.
Figure 5 Testosterone (or anabolic-androgenic steroids) binds to the androgen receptor in the cytoplasm and the complex moves into the nucleus where it interacts with DNA to initiate protein synthesis.