Much leptin research in humans has focused on feasting rather than famine, but Christos Mantzoros’s team, led by Jean Chan, a Harvard Medical School clinical fellow in medicine, took a different approach.
Mantzoros, lead author and HMS assistant professor of medicine at BIDMC, and his group studied eight healthy men to see how the changes in leptin induced by fasting regulated other neuroendocrine signals in normal humans. The men spent four five-day sessions in the BID General Clinical Research Center, during which time they ate a normal diet that would maintain their weight and establish a baseline of hormonal levels, fasted for three days out of two sessions, were injected with a placebo, given low doses of recombinant human leptin, and given doses of recombinant human leptin that achieved normal levels.
During the brief periods of starvation, the men experienced a significant drop in testosterone levels as expected, along with a drop in leptin. But replacing leptin to physiologically normal levels during fasting fully restored testosterone to baseline, indicating that leptin regulates the hypothalamic-pituitary- gonadal axis that controls the release of testosterone and estrogen.
The study also suggests that leptin may regulate thyroid hormone. “Leptin clearly has some effect on the thyroid hormone axis,” said Chan, including thyroid-stimulating hormone and the free-circulating form of thyroid hormone.