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Testosterone and Fat Loss- Greater Benefits Than Realized |
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Written by Dan Gwartney, MD
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Sunday, 04 January 2009 |
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Page 3 of 5
Genomic Effects
In the broadest sense, it can be stated that androgens are anti-adipogenic, while estrogens are pro-adipogenic.3 In other words androgens (such as testosterone) reduce body fat stores and the development of new fat cells, while estrogens promote fat storage and development.
This isn’t surprising, considering the clear differences between male and female bodies. Beyond recognizing this fact, it’s important to understand why this difference exists if one is to try to manipulate body fat stores pharmaceutically. The classic understanding of steroid hormones is relatively straightforward. Essentially, a steroid crosses the cell membrane, links up with a receptor that’s floating within the insides of a cell and the pair travels to the DNA. The steroid-receptor pair turns on certain genes, which create new proteins or alter cell function. But like all things in life, it’s actually more complicated than that. Steroids do cross into the interior of a cell and associate with receptors in order to travel together as a pair to the DNA. However, there are many different co-modulators, molecules which change the effect of the steroid-receptor pair, either increasing or blocking the effect on the DNA. Receptors are also embedded in the cell membrane, which bind to steroids.7 These membrane-bound receptors don’t travel to the DNA after linking with steroids; rather, they alter the cell’s sensitivity to other hormones. The scientific literature refers to the DNA-associated changes as genomic effects and the membrane-bound changes as non-genomic effects.
In order to assign any effect in fat cells to steroids, it was first necessary to prove that fat cells contained steroid receptors. This has been proven for androgens, estrogens and progesterone.8,9 Interestingly, different areas of fat have different concentrations of sex steroid receptors. Androgen receptors are highest in intra-abdominal fat, while estrogen and progesterone receptors are highest in gluteal fat regions.10,11 The steroid receptors are sensitive to steroid levels and increase in number when steroid levels rise.9,10 This is very interesting as it explains why greater effects are seen in supraphysiologic anabolic steroid cycles and why aging men seem to have such difficulty keeping fat off. In the first case, fat cells are more sensitive to androgens when exposed to higher levels. In the second, not only do steroid levels fall, but the aged male is less sensitive to the hormones. The fat loss effects of androgens appear to involve both genomic and non-genomic processes. Classic steroid receptors allow steroids to affect the formation of new proteins, such as enzymes and hormones. Lipoprotein lipase and leptin are two examples of genomic control of fat balance by steroids. Lipoprotein lipase (LPL) is an enzyme released by fat cells that breaks down triglycerides (fats) circulating in the blood, so it can absorb the free fatty acids and glycerol components of these triglycerides.12 It’s been theorized that by decreasing LPL, lesser amounts of free fatty acids would be available to be absorbed by the fat cell, preventing a gain in fat stores. Studies involving other hormone seem to support this, as LPL rises with cortisol and insulin— two hormones known to increase fat stores; and is lowered by growth hormone— a fat-reducing hormone.13 In women, this may be true, as estrogens given as hormone replacement to menopausal women reduce LPL levels and fat loss has been documented. Androgens (testosterone) actually increase LPL levels in women.14 In men, testosterone has the opposite effect, reducing LPL levels.15 This effect was not seen with the more potent androgen, DHT, leading researchers to investigate the possible role of aromatization. Aromatization is the enzymatic process by which testosterone is converted into estrogens. Aromatase is present in human fat cells.16 It was discovered that the LPL-lowering effect of testosterone isn’t present when aromatase is blocked. Given that DHT doesn’t consistently affect LPL and that the LPL-lowering effect isn’t seen when an aromatase inhibitor is present, it’s evident that the LPL-lowering effect of testosterone is due in part to its ability to act as an estrogen precursor.17 It isn’t understood why this discrepancy exists between males and females, but it demonstrates the need to consider gender when studying steroid effects.
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Research and Review 
