Tag Archives: sexual desire

When I’m Sixty Five

Special dedication to

Jacques Balthazart!

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birthday greetings

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Pictured, a Valentine, a birthday greeting, a bottle of wine, and a Jupiler

Jacques Balthazart is a true leader in behavioral neuroendocrinology, the study of how hormones affect the brain and behavior. His retirement demanded a fitting tribute, but there was a problem. When it comes to international conference organizers, nobody does it better than Jacquesyoung jacques Balthazart. So, who would throw this party? No worries. The Belgian government’s policy requiring mandatory retirement at age 65 turned out to be the catalyst for a nonpareil scientific meeting (throughout this blog, all words underlined are links). It also turned out to be an outrageous birthday party and a creative plan to continue research on his own terms. Last week, the combination of foundational research, cutting-edge science, Belgian beer, and collegiality led to the conference’s new nom de plume: The International Conference Honoring Brilliant Balthazart (ICHBB).

Jacques is shown above and to the right just moments before the party, and below, just a few days into the party.

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Photo by GianCarlo Panzica of Jacques Balthazart, 65,  in a gift hat symbolizing his dual loyalty to Belgium and the U.S.
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ICHBB Conference photos by GianCarlos Panzika

After all, when you are the premier conference organizer, entertainer, and hub of your scientific community, it makes sense that you should plan, host, and orchestrate your own birthday retirement party!

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“Team Jacques” adapted from a funny photo by Julie Bakker

The first ICHBB was named the International Conference on Hormones Brain and Behavior and held in Bielfeld, Germany in 1982. It was conceived and developed from Jacques’ isolation as one of the few behavioral endocrinologists in Belgium. His uncontrollable desire for scientific interaction led him to invite about 40 premier behavioral endocrinologists from around the world to Bielfeld. To his surprise, they all showed up; it was an unqualified success; and everyone wanted to do it again and again. And again. In subsequent years, Jacques personally nursed the ICHBB in his home town of Liege (in 1984, 1989, and 2014) and affectionately nurtured the conference when it was hosted by others in France, Italy, and Spain.

liege buttfly bushes  2 I learned some things about Jacques’ life that I hope will be shared, remembered, and handed down to our academic offspring! First, necessity is the mother of invention in that some of Jacques’ biggest contributions to science come from his ability to embrace his authentic small-town lifestyle while uniting the world of behavioral neuroendocrinology. He was born, raised, educated, bred, and “retired” in Liege, Belgium, far less a tourist destination than a very pleasant place to grow up, and Jacques truly loves Liege. Many Americans have never even heard of Belgium, let alone, Liege, but one thing is very clear. Liege is “on the map” in the minds of behavioral endocrinologists. This just shows that there is no point in whining about where you work. I know behavioral endocrinologists at big U.S. medical schools, at Yale, or in big universities like UC-Berkeley who feel more isolated than Jacques.

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Scenes from Liege

 

 

 

 

 

 

 

 

 

 

 

 

 

This idea was confirmed by plenary speaker, Kathy Olsen, former deputy director of the National Science Foundation, chief scientist for NASA, and associate director and deputy director of science in the executive offices of the President of the United States of America. According to Kathy, there is no one else to blame for putting Liege on the map other than Jacques Balthazart.

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Kathy Olsen (right) shown with Vicki Luine and Yasuo Sakuma (left)

In terms of hormones and behavior, Jacques brought the world to Liege. I was surprised to learn that the man we know as the hub of our global science community is very much a local family man. Jacques’ father was a local architect, and his mother worked as a full-time homemaker and mother of two children. Jacques was educated from primary school on up through college in his home town of Liege. It was at the University of Liege that he fell in love with one of his biology professors, the beautiful and enviably fit, Claire (apparently she still runs 10K a day!). In addition to having a successful career in biology, Claire is a super friendly, social, community-oriented woman-about-town. Jacques, on the other hand, is not nearly as involved with his local friends and relatives. Though Claire chides Jacques for not remembering neighbors who have known Jacques his whole life, Jacques, ironically, is the social glue holding together a giant global network of scholars and friends, many of whom traveled far and wide to celebrate Jacques’ birthday. In one of Jacques’ presentations this week, he showed a world map dotted in every continent with markers showing where he has friends who will meet him at the airport.

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Lauren Riters and family (left) and Nicole Cameron with a lot of French stripes (right)

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Nicole, Lauren, Lauren’s son, Nancy Forger and Geert DeVries (left) and cannibals on the menu (below)

A Bad Bromance

Everyone in behavioral endocrinology knows that Jacques Balthazart has co-authored numerous landmark articles with Greg Ball, begging the question “How did this fertile collaboration begin?” During the various tributes at the conference, we learned that in 1983, Greg Ball was a graduate student at the Institute for Animal Behavior at Rutgers-Newark, where Jacques Balthazart was a distinguished visitor. Jacques, however, was not impressed with that Greg Ball character!

Jacques recalls Greg as a “lazy, long-haired hippie hanging around drinking coffee and pontificating in the break room all day long in a booming voice that could be heard all over the department.” As they say, first impressions are the best. Well, except the lazy part, because Greg’s and Jacques’ publications together number at least 400, and somewhere between 110-115 of those articles are co-authored by Ball and Balthazart or Balthazart and Ball.

The Ball and Balthazart Bromance was finally consummated (scientifically) a few years later in Germany. Greg Ball, then a postdoc with John Wingfield, was invited to speak at the conference. Greg was put up in a small dormatory-like room with a single bathroom shared by the adjacent room. Greg was brushing his teeth when his new next door neighbor, Jacques Balthazart, burst into the bathroom. “Well, well, well, we meet again!” Only this time, the Greg-Jacques Belgian beer bromance began in earnest (Wait? Who’s Ernest?) From the time of that meeting, Jacques Balthazart and Greg Ball became fast friends and insanely productive collaborators.

Incidentally, you can trace the academic family trees of these characters and that of your own mentor at Neurotree.org. Greg Ball’s tree is probably the most interesting, reaching straight back to Niko Tinbergen and Konrad Lorenz.

Peg McCarthy, Greg Ball’s beloved spousal unit, in her plenary lecture, explained that Jacques was a daunting obstacle blocking Greg’s affections for Peg in the initial stages of their courtship. At first, it was clear to Peg that Jacques would always be Greg’s “first wife.” It seemed she could never compete with Jacques. Luckily, Jacques came to adore Peg, and now warmly accepts Peg as a sisterwife. Suffice to say, that if all sisterwives were like Jacques and Peg, we would all be Mormons.

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Greg Ball and Peg McCarthy (left) and a nicer pic of Peg with me and Colin Saldanha

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   Celebrating Belgium Moving Up In the World Cup 2014

To Sir Jacques With Love

The entire meeting was infused with enormous gratitude and affection from Jacques’ present and former students, postdocs, collaborators, family, and friends. Greg Ball gave a “What I learned from Jacques” speech that I wish all graduate students could hear. The highlights included

1) PUBLISH all of your data immediately. You never know when or how your results will be useful to other scientists, and none of it will matter if it is not published.

2) Time is precious, so, collect data, and write without fail, regardless of how late you stayed up the night before. No excuses. As Jacques would say, you have one 33 cl (Jupiler) at lunch and then bike back to work!

3) Be brave about methods. If it’s been done, you can do it.

4) Good ideas come from many sources, so, go to meetings and host your own.

5) Good colleagues can be good friends.

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Jacques and Jeff Blaustein are not at all faking interest in my poster presentation. Photo taken by Vicki Luine.

In any case, there were so many excellent talks and posters at the meeting, demonstrating that Jacques will live on through his scholarship and mentoring as long as human civilization survives. Happily we learned that Jacques will continue working at the University of Liege, without the unpleasant duties of his old position, but instead intensifying focus on the research that he loves. This is one of the benefits of launching the careers of young, outstanding scientists and scholars. Shown below are ICHBB attendees who came to honor Jacques: Dave Grattan, Colin Saldanha, Kiran Soma, Jim Pfaus (with son, Josh), Thierry Charlier, Chuck Roselli and many others in the group photos.

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Enjoy the next phase, Jacques! Your work is alive and well in all of our research programs. See you soon.

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The above photo of Jacques and the preceding six were taken by GianCarlo Panzica.

There will be more pictures available through the website for the ICHBB. Meanwhile, you will find some links to seminal Balthazart discoveries here and here.

And finally, here’s a funky version of what I’m sure Jacques’ mentees are thinking…

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Happy Fat Tuesday from Schneider Lab

As Fat Tuesday approaches, my mind turns to cycles of indulgence and moderation. This is not news to women. They are quite familiar with regular, repeated bouts of uncontrollable appetite. Women are more prone to obesity and binge eating, and their binges are more likely to occur at a certain phase of the menstrual cycle. These differences are related, at least in part, to changes in hormones secreted from the ovaries. The ovaries secrete steroid hormones, such as estradiol and progesterone. Changes in estradiol and progesterone secretion alter the steroid environment in the brain and body, so that when hunger strikes, we might feel “just peckish” at one stage of the menstrual cycle or ravenously hungry at another phase.

How does this work? I received a four-year research grant from the National Science Foundation in 2013 to study ovarian hormone effects on appetite.

One clue to understanding estradiol is that it affects sexual desire and hunger for food in the opposite direction. 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 peaks (although sexual activity can occur any time during the menstrual cycle). As women approach menstruation, progesterone levels and the appetite for food rise 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).

So, changes in hunger for food are correlated with changes ovarian steroid hormones, but correlations cannot tell you what causes what. My work started by looking for brain hormones secreted by cells with steroid receptors, brain hormones that increase the appetite for food and decrease the desire for sex. The problem is, we can’t really muck around in our own brains to study these hormones (neuropeptides). It’s difficult 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 desire. No thanks. I like to study Syrian hamsters because I can precisely control 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), when we give them back their food, they increase their food hoarding. The hungrier they are the more food they carry in their cheek pouches from a distant source to their home cage. We can measure hamster sexual desire and hunger for food quite easily and accurately.

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Hamster food hoarding (mean and s.e.m.) over the four days of the ovulatory cycle in food-restricted (open triangles, dotted lines) and food-unlimited (solid circles and lines) females housed with the choice between staying home, visiting a male, or hoarding food. The predominant sex behavior of the food-restricted female is shown in a cartoon above the hoarding data. On day 4 of the cycle, the periovulatory day, the females show mating behavior. On day 3, they show vaginal scent marking but do not mate. On days 1 and 2 they spend more time hoarding food than visiting the male. (Adapted from Klingerman et al., 2010 by Jay Alexander)

            Candice Klingerman (a former grad student in my lab at Lehigh University and now a real professor at Bloomsburg University), found that hamsters on calorie-restricting diets show little interest in males and spend most of their time busily hoarding food, except on the day of ovulation. As ovulation approaches, however, they spend more and more time near the males. What you might find surprising is unrestricted females are obsessed with males throughout the ovulatory cycle! Whether they are ovulating or not, they ignore the food and spend more than 75% of their time leaving vaginal scent marks near the males. Like most rodents, they mate only on the day of ovulation, but the chubbier, calorie-unrestricted females prefer males over food every day of their four-day cycle. The differences between the calorie-restricted and unrestricted females are illustrated in the graph to the right, where you can see that calorie-restricted females do lots of food hoarding on most days of the cycle, with a conspicuous dip at the time of ovulation. The unrestricted females’ hoarding levels are low and flat throughout the cycle because they spend most of their time with the male (Klingerman et al., 2010).

You can see from the figure above that living in an “all-you-can-eat” buffet masks the effects of the ovarian cycle on the appetites for food and sex. Females on the “all-you-can-eat” diet consistently prefer to court males rather than stock their larder with food. Those females that are calorie-limited save all their sexual ardor for the small window of fertility on the day of ovulation. They spend the rest of the ovulatory cycle busily hoarding food. In the wild, this would ensure that there will be plenty of energy available for their offspring if their mating results in a pregnancy. This result makes me wonder whether our understanding of sex hormones has been clouded by studying animals housed in small cages with unlimited food. It makes me wonder how much our own species has diverged from our ancestors, now that we have adopted a sedentary lifestyle with food available in office vending machines, coffee break rooms, fast food restaurants, and well-stocked homes. No wonder we sit around watching Game of Thrones.

What are the brain differences between the hamsters on a limited-calorie diet and the hamsters at the “all-you-can-eat” buffet? I suspected that I would be able to find a brain hormone (neuropeptide) secreted by cells that have steroid receptors. I further suspected that the secretion of this neuropeptide is increased by food restriction. A review of the literature revealed many such chemicals. I have posted a handy table in a previous blog post here.

At the moment, we are interested in gonadotropin inhibiting hormone, GnIH. The figure below shows a hamster brain cell (neuron) that produces GnIH (a neuropeptide), which is stained red. Those GnIH cells that were activated by food restriction are shown in red with a green/yellow dot in the middle. These are cells labeled for GnIH and Fos, a marker for cellular activation. 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.

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Brain cells stained for GnIH (red) and Fos (green). The red stain represents GnIH which occurs in the cytoplasm and thus colors a wide area of the cell body. The greed stain represents the proto-oncogene product Fos, a protein that is synthesized upon cellular activation. Fos resides within the cell nucleus. Cells that are red with a green/yellow stained nucleus are double-labeled with GnIH and Fos. These represent GnIH-containing cells that have been activated by food restriction. (Photograph and immunohistochemistry by Noah Benton)

Some of my other great colleagues in Australia (e.g., Iain Clarke) were showing that GnIH increases food intake in sheep, monkeys, and rats. GnIH sounded promising. Thus, I approached Lance about studying the effects of GnIH on the appetites for food and sex in Syrian hamsters. My student Candice Klingerman partnered with a grad student from the Kriegsfeld lab, Wilbur P. Williams. Together, Klingerman and Williams found that the level of calorie restriction was a good predictor of the level of GnIH cell activation (Klingerman, Williams, et al., 2011).

           This suggested that GnIH might be part of the system that orchestrates the appetities for food and sex. This was confirmed by Noah Benton (Lehigh) and David Piekarski (UC-Berkeley). They administered GnIH to the brains of well fed females, and found that the GnIH-treated hamsters acted like they were starving. Their sexual appetites were lowered and their hunger for food was increased by GnIH treatment in the brain.

            Another prediction you can make based on the hoarding data shown above is that GnIH will have different effects depending on the day of the ovualtory cycle (and the levels of estradiol and progesterone secreted from the ovary). Consistent with this idea, 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 above, 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 activated. Noah double-labeled cells for both Fos and GnIH in food-restricted and food-unlimited females on every day of the ovulatory cycle. On nonfertile days of the cycle, there are significantly more GnIH cells activated in food-restricted compared to food-unlimited females. As you would predict from their sexy behavior, however, on the day of ovulation, GnIH is not elevated by food restriction. Go, Noah!

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. Will it be estradiol, progesterone, or testosterone? Place your bets.

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 important function of these hormones is to orchestrate the appetites for food and sex, perhaps to maximize reproductive success in environments where energy availability fluctuates. These effects are short-lived and change rapidly in the small time window of fertility (basically 1 day of the 4-day ovulatory cycle). It is probably unrealistic to expect any one of these neuropeptides to be a long-term or permanent cure obesity. Maybe we should think more broadly about how all this obesity has come about, and put some energy into understanding the link between energy balance (food intake, body fat storage, and energy expenditure) and reproduction.

Meanwhile, happy Mardi Gras!  http://www.youtube.com/watch?v=mcNJpIp8w0Y 

             

           

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March 1, 2014 · 4:40 pm