Selective thyroid boost may cut cholesterol, reduce weight

Monday, July 28th 2003, 12:00 am

By: News On 6

WASHINGTON (AP) _ A chemical that boosts the effectiveness of a thyroid hormone may one day help people lose weight and cut cholesterol without the rapid heartbeat sometimes associated with thyroid stimulants.

The findings, while still preliminary, could have major implications in a nation increasingly worried about obesity.

Thyroid hormones are known to help in weight loss by stimulating metabolism _ and cutting cholesterol _ but come with the unwanted side effect of speeding up the heartbeat.

The activity of these hormones is regulated by chemicals called hormone receptors. A team of researchers has found a way to encourage one of them, but not the other, eliminating the dangerous heart side effect.

The findings of the team led by Gary R. Grover of the Bristol-Myers Squibb Pharmaceutical Research Institute are reported Monday in the online edition of Proceedings of the National Academy of Sciences.

Dr. Jules Hirsch of Rockefeller University, who was not part of the research team, called the report ``hopeful in a very early stage.

``This is a valid and important and interesting piece of research,'' he said, which reopens an area of study with better tools that scientists have had in the past.

More long-term animal studies are needed to see if the hormone receptors adapt in some way, Hirsch added. Grover has worked with mice, rats and monkeys.

While most research into obesity has focused on appetite suppression, Grover said he decided to look for ways to help burn more energy, but do it in the safest way possible.

``This is really a novel way of looking at obesity,'' he said.

``It's an interesting and intriguing finding, but it needs more investigation,'' added Brian Henry of Bristol-Myers Squibb.

Grover stressed that he is not administering thyroid hormones, which is permitted only for patients whose thyroids do not function properly.

The goal, he said, is to develop a treatment to assist obese people with normal thyroid function.

Hormone receptors that facilitate the action of thyroid hormones are divided into two main types, Grover's team reported. Receptor-a seems to be more important in regulating heart rate while receptor-b is involved in cholesterol lowering and metabolism.

They found a chemical called KB-141 that encourages the action of receptor-b many times more strongly than receptor-a.

Whole body oxygen consumption, a measure of metabolism, was increased in animals given KB-141 and the monkeys had a 7 percent loss of body weight in a week without affects on the heart, the researchers reported.

Grover said he is continuing to work with KB-141 as well as other compounds to see if they will have similar effects.