|Volume 10, 2014 - Biological Sciences Newsletter - Spring 2014|
Our Research .....
by Jill Schneider, Ph.D.
Most people these days are struggling to control their weight gain, but if you are a woman, you might notice that you go through regular, repeated periods when your appetite seems virtually uncontrollable. Women are more prone to obesity and binge eating than men, and their binges are more likely during a certain phase of the menstrual cycle. These differences are in part related to changes in hormone secretion from the reproductive organs, the ovaries. The ovaries secrete steroid hormones, such as estradiol and progesterone. Menstrual cycle changes in estradiol and progesterone secretion alter the steroid environment in the brain, so that when hunger strikes we might feel either “just peckish” at one stage of the cycle or ravenously hungry at another phase. After menopause, when estradiol levels fall, it might be next to impossible to lose weight. How does this work? My laboratory group just received a four-year research grant from the National Science Foundation to study how these ovarian hormones control appetite.
One clue is that estradiol has the opposite effect on sexual desire. In the middle of the menstrual cycle, when estradiol levels are highest, the appetite for food falls to its lowest level. This is the time when females are most fertile and sexual desire is at its peak. As women approach menstruation, the appetite for food rises while sexual desire tends to fall. Similarly, after menopause, as the ovarian hormones wane so does sexual urgency (to different degrees, depending on the individual).
Given these clues, I suspected that there is a brain hormone that might increase the appetite for food, decrease the desire for sex, and have different effects depending on the levels of estradiol and progesterone secreted from the ovary.
It’s virtually impossible to study human food intake and sexual behavior because people lie about how much and what they eat. Don’t even get me started on measuring their sexual activity. I like to study Syrian hamsters because I am in control of what they eat, and they ovulate like clockwork every 4 days, unlike women who ovulate every 24-32 days. Plus, hamsters have a great way to demonstrate their hunger.
After a period of dieting (say, we feed them only 75% of their normal daily food intake for a week), they increase their food hoarding. They carry food in their cheek pouches from a distant source and hide it in their home cage. We can measure both sexual desire and hunger for food quite easily and accurately.
One brain hormone we are studying is GnIH (gonadotropin inhibiting hormone). The figure to the right shows a hamster brain cell (neuron) that produces GnIH (a neuropeptide), which is stained green. I got interested in GnIH when my colleague, Lance Kriegsfeld at the University of California at Berkeley, showed that GnIH inhibits reproduction in Syrian hamsters. Thus, I approached Lance about studying the effects of GnIH on the appetites for food and sex.
Together, our graduate students Candice Klingerman (Lehigh) and Wilbur Williams (UC-Berkeley) found that hamsters limited to 75% of their normal food intake showed very high levels of sexual motivation and very low levels of food hoarding, but only at the time of ovulation. As predicted, the activity of GnIH cells was quite low at this time. When females were at the nonfertile periods of the cycle, food restriction induced very high levels of food hoarding with no interest in sex, and this high interest in food vs. sex was associated with increased activation of GnIH cells. What some people might find surprising is that in females fed as much food as they wanted, sexual motivation was high and food hoarding was low over the entire ovulatory cycle!
When Noah Benton (Lehigh) and David Piekarski (UC-Berkeley) administered GnIH to the brains of well fed females, the hamsters acted like they were starving. Their sexual appetites were lowered and their hunger for food was increased by GnIH treatment in the brain.
My student, Noah Benton, is finding that in food-restricted females, the activity of GnIH is elevated only during the nonfertile periods of the female cycle. In the figure below, GnIH cells are shown in red, and the activation of those cells is indicated by the central dot stained green for Fos, a protein that shows up in cells that have been activation. GnIH activation is elevated in the nonfertile period, but is not elevated by food restriction at the time of ovulation, when females are fertile, sexually aroused, not interested in food, and ready to optimize their chances of getting pregnant and contributing their genes to the next generation.
GnIH activity is usually elevated in food restricted females, except at ovulation. We think the effects of GnIH are dampened by one of the hormones that is high around the time of ovulation. Noah Benton’s dissertation work will determine which ovarian steroid hormones and receptor are important for these effects.
Many obesity researchers think that appetite suppressing hormones are suppose to function to preserve our youthful figures and keep our body weights in fashionable and healthy limits. The work of my students shows that an unsuspected function of these hormones is to orchestrate the appetites for food and sex so as to maximize reproductive success. These effects are short-lived and change rapidly in the small window of fertility. It is probably unrealistic to expect one of these neuropeptides to be a long-term or permanent cure of obesity. Our work demonstrates that basic information about hormones and the brain is critical for the application of data to clinical problems.
Murray Itzkowitz, Chair | Michael Behe | R. Michael Burger | Lynne Cassimeris | David Cundall