Researchers Pinpoint Brain Signals Linking Low-Calorie Diet To Infertility

November 1, 1996

GAINESVILLE—Scientists have long known that dieting, fasting and malnourishment can cause at least temporary infertility in women and men. Now, for the first time, they think they know how.

Researchers at the University of Florida Brain Institute say the culprit appears to be faulty signals emitted by the brain’s elaborate nerve communication system that controls both appetite and reproductive function.

The signal or chemical trigger, they report in the October issue of the scientific journal, “Frontiers in Neuroendocrinology,” is the abnormal activation of at least three interconnected networks of nerve transmitters in the brain.

These neurotransmitters — the brain peptides NPY (neuropeptide-Y), galanin and opioid — are essential messenger molecules in cell-to-cell communication in the hypothalamus, the higher brain center regulating several body functions including hunger, sex drive and reproduction.

“We’ve known for years that nutritional imbalance for short periods of time, such as during dieting or fasting, can suppress reproductive function and sexual behavior. Until now, though, we didn’t know how these two functions were interconnected in the brain,” said Satya Kalra, professor of neuroscience at UF’s College of Medicine and a faculty member of the university wide brain institute. “We’ve managed to decipher the chemical mechanisms in brain nerve cells that allow nutritional signals to alter the brain’s control of reproductive behavior.

“Mapping the site of these signaling mechanisms makes it a target for future drug therapies designed to reverse or prevent nutritional infertility.”

Kalra had determined NPY’s leading role in governing appetite and reproduction in landmark studies in rats in the mid-1980s. NPY was shown to stimulate appetite at one site of the brain and control the sex-hormone secretion at another. He discovered that abnormally high or reduced secretion of this peptide may produce eating disorders such as obesity or anorexia

nervosa, and may lead to reproductive failure in both men and women.

In his most recent studies, analysis of rat brains revealed shared nerve pathways and a close interplay among NPY and the peptides galanin and opiod. The chemical compounds, all vital to communication between nerve cells, are found in the brains of both rats and humans.

Kalra also reported his findings recently at a national symposium on nutrition and reproduction in Baton Rouge, La.

What do the findings mean to health consumers?

Besides NPY’s influence on reproduction during periods of low food consumption, increased NPY action also appears to play a role in impaired reproductive behavior among diabetics, lactating or nursing mothers and obese people, Kalra said.

Scientists are gaining a better understanding of NPY’s disruptive influence, which can speed the development of ways to treat so-called nutritional infertility.

Kalra’s report also offers some good news to exercise buffs. Strenuous exercise alone, without accompanying food restriction (or “caloric imbalance” as scientists call it), is unlikely to impair one’s reproductive system, he says.

“The apparent association between strenuous activity and reproductive failure may result from nutritional changes due to either poor nourishment or short-term imbalance between food intake and the body’s energy expenditures.”

Based on Kalra’s earlier work, scientists elsewhere recently identified the NPY system as the triggering mechanism for leptin, a protein produced by the gene controlling obesity. Disruptions in the production of this protein has been found to increase NPY secretion in the brain, leading to increased appetite and obesity.

“Now scientists know where to look for leptin production and where to look for causes, so we can get a handle on obesity,” Kalra said. “Future efforts to further define the influence of this interconnected system of neuropeptides could help us better understand and treat suppressed reproductive function associated with a variety of eating and energy-metabolism disorders.”