Nuclear receptors are proteins found inside cells that sense steroid and thyroid hormones and certain other molecules. Androgen receptors (AR) are nuclear receptors that sense and act on androgen, a hormone vital to male sexual development such as puberty. Androgen receptors respond to androgen hormones by binding to them which in turn attaches to the person's DNA.
Its role is to regulate the activity of androgen-responsive genes by activating or deactivating them. This helps the AR to regulate and direct the development of male sexual characteristics as well as functions in both males and females such as hair growth and sex drive.
Glucocorticoids
Glucocorticoids (GC) are natural occurring steroids that regulate the metabolism of glucose and its synthesis in the adrenal cortex.
GCs are used by the immune system to slow down or turn down immune system activity such as inflammation. These steroids also have the ability to control, regulate, and sometimes interfere with the internal mechanisms of cancer cells.
Because of these properties, glucocorticoids are used heavily in medical treatments that range from cancer therapy to autoimmune diseases. Despite the positive benefits GC properties have, it also has many other effects that may prove harmful when used without proper medical supervision.
A side effect on the use of glucocorticoids is that it can increase weight gain by encouraging fat buildup and appetite stimulation.
Manipulating hormone receptors may help in the fight against obesity
In the body's ongoing effort to maintain a healthy weight, an arsenal of cellular proteins called androgen receptors is critical for blocking fat accumulation. Now researchers reporting in the September issue of the Cell Press Journal Chemistry & Biology have discovered that naturally occurring steroids called glucocorticoids can thwart the receptors' activity, ultimately encouraging fat buildup.
"This has implications in this era of an obesity epidemic," says senior author Dr. Michael Mancini, from Baylor College of Medicine. "If you can reduce glucocorticoids, you might be able to upregulate, or increase, androgen receptor activity and regulate fat storage."
Video: Physiologic Actions of Glucocorticoids
The discovery came after Dr. Mancini and his team searched for genes or signals expressed specifically by human fat cells with the hope of gaining a better understanding of fat deposition and the development of obesity. They used a novel approach that combined gene expression studies with automated microscopy and specialized image analyses.
The approach showed that the androgen receptor is both expressed and functional during the early stages of fat cell differentiation. "Activation of the androgen receptor can inhibit the early stages of human fat maturation," says first author Dr. Sean Hartig, also from Baylor College of Medicine. The finding makes sense because androgens such as testosterone, which bind to androgen receptors, are known to favorably direct muscle differentiation, regulate muscle mass, and increase lean body mass as humans age.
The researchers also found that glucocorticoids decrease androgen receptor activity and alter the effects of androgens on fat storage. The result is deposition of fat throughout the body, particularly in the abdominal region. "Using a custom-developed image analysis software platform usually found only in large pharmaceutical screening centers, we applied specific algorithms to sensitively detect the glucocorticoid inhibition of androgen receptor activity," says Dr. Mancini.
The research suggests that treatment strategies that modulate the activity of glucocorticoids and the androgen receptor—perhaps in combination—may help combat obesity.
RELATED LINKS
Cell Press
Chemistry & Biology
Baylor College of Medicine
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