By Joe Grossman

BALTIMORE, Oct. 14 (UPI) - - A gene in mammals known to play a crucial role in the maintenance of hair growth has long been known to exist. In rare cases the gene malfunctions and results in the inability of hair to grow normally, resulting in complete baldness. However, the exact way in which this happens has remained unclear. Researchers at the Kennedy Krieger Research Institute at Johns Hopkins University School of Medicine, Baltimore, have now shown part of the mechanism by which this happens.

The gene is called the hairless gene. When it is functioning properly, hair growth is normal. But in its variant mutated form a person can have varying degrees of baldness.

The hairless gene produces a protein that binds to a molecule known as the thyroid hormone receptor. The thyroid hormone receptor regulates expression of specific target genes and controls whether they are turned "on" or "off." Under conditions with relatively little thyroid hormone present, such as in the early years of life, thyroid hormone receptors repress (or "turn off") expression of these target genes. The binding of the hairless protein to thyroid hormone receptors mediates the ability of these receptors to turn off gene expression. Mutation of the hairless protein likely disrupts expression of these target genes, resulting in the varying degrees of hair growth reduction.

The new discovery of this work is the specific way in which the protein produced by the hairless gene binds to the thyroid hormone receptor, resulting in the regulation of gene expression. This detailed information may open the door to fashioning some form of intervention for both rare congenital and common hair loss disorders.

One of the researchers, Catherine C. Thompson, told United Press International, "We've discovered what the function of the protein encoded by the gene is. The gene's been known for several years now, but you can't predict what the protein encoded by the gene does, based upon its sequence, so it really was quite a mystery." Thompson, an assistant professor at Johns Hopkins University School of Medicine, Baltimore, said, "Our work has shown that (the protein) acts as a transcriptional corepressor, which shows what the protein does . . . When it doesn't work properly, the bottom line is that you get hair loss." Transcriptional corepressors rachet down gene function in cooperation with other proteins. The findings will appear in the October 15 issue of Genes & Development, a publication of Cold Spring Harbor Laboratory Press.

Gregory A. Brent, associate professor of medicine and physiology at the UCLA School of Medicine told UPI that thyroid hormone, estrogen and testosterone all influence hair growth and hair loss and affect other tissues such as bone development and growth. People with hypothyroidism, (underactive thyroid gland) can develop dry and brittle hair and often have hair loss. "The identification of an interaction between hairless protein and thyroid hormone receptor in gene regulation by Dr. Thompson, is an important link between these clinical observations and the molecular mechanisms of hair loss," Brent said.

According to Brent there is a rapidly developing field of thyroid hormone receptor activators and repressors that could potentially influence the interaction of hairless protein mutations and the thyroid hormone receptor. "These compounds, as well as the development of topical thyroid hormone administration, could provide important therapeutic targets in hair loss," Brent added.

Joshua Safer, an endocrinologist specializing in thyroid disease and an assistant professor at Boston University School of Medicine Research told UPI, "Dr. Thompson has described a new corepressor which acts in specific tissues or in specific gene pathways." Safer said that this is important because up until now most of the biochemical pathways described have been quite general.

"If there are abnormalities with regard to them or diseases that are affected by them it's not been clear how one would target them without affecting a huge number of unrelated genes or tissues. What's special about this is that it's very specific . . . If there are abnormalities with regard to this corepressor one can imagine some mode of compensating that is specific to the problem and would not affect other genes or other tissues," Safer said.