Researchers find genes connected to seasonal reproductive clock in hamsters

Researchers at Ohio State University have identified three genes that are involved in the seasonal clock that determines when hamsters reproduce.

While researchers have learned a lot about reproductive clocks in some animals, this study is unique in helping uncover at least part of the genetic basis for determining how the reproductive system shuts off in the fall and restarts in time for spring.

“This study offers some of the first insights into how changes in gene expression are associated with a seasonal clock,” said Brian Prendergast, co-author of the study and a post-doctoral fellow in psychology at Ohio State University.

The study was published online last month and will appear in the Dec. 10 issue of the Proceedings of the National Academy of Science.

The researchers found that the three genes – transthyretin, T4-binding globulin, and albumin – were turned on or off as part of an internal clock in hamsters. These genes help regulate levels of thyroid hormones in the hypothalamus, which is involved in controlling the hamsters’ reproductive cycle.

Hamster reproductive cycles are tied to day length and the amount of daylight they are exposed to during part of the year, Prendergast said. But there’s an interesting catch.

As daylight shortens in the late fall and early winter, the reproductive organs of the hamsters respond by shutting down. In the male hamsters used in this study, the testes regress as daylight shortens. However, the reproductive system begins to turn back on in mid-winter – long before daylight starts to lengthen. The reason why this has to happen is simple: it takes one to two months for the reproductive system to redevelop and if the hamsters had to wait for the lengthening days of spring to start the process of regrowth, it would be too late.

“The short days of winter triggers a timer that shuts off the reproductive cycle,” Prendergast said. “But the timer ends in mid-winter and tells the brain to stop responding to the short days. That’s when the reproductive cycle starts again.”

The researchers found part of the genetic basis for why the reproductive system is able to turn back on in the middle of winter.

In their experiments, the researchers had three groups of hamsters. One group was kept in long days – such as they would have during the summer when they are reproducing – for the whole 32-week experiment. Others were kept in short days during the whole experiment. The third group was kept in long days for 20 weeks, then moved to short days for the final 12 weeks.

The researchers were interested to see what was happening in a part of the brain – called the hypothalamus – that plays an important role in controlling reproduction in hamsters.

After the 32 weeks, the researchers sacrificed the hamsters to see which genes were active in the hypothalamus and which were not, and whether it differed depending on what season the hamsters were kept in.

The results showed that the three genes were being expressed – in other words, they were turned on – in the hamsters that were kept constantly in short days or in long days. These genes produce proteins that help the hypothalamus take in thyroid hormones involved in the regulation of reproduction. In other words, the animals in both long and short days had high levels of thyroid hormones in the brain and therefore were able to respond to changes in day length.

That’s because hamsters need these thyroid hormones both when they are breeding and when the reproduction system shuts down in the winter. Prendergast explained that a different process – separate from the thyroid hormones examined in this study – seemed to be involved in shutting the reproductive system down for the winter.

But the researchers found that the hamsters also need thyroid hormones in the hypothalamus to keep the reproductive system shut down during the winter. If the hypothalamus does not continue to get these hormones, the reproductive system beings to automatically re-grow. So when mid-winter comes the internal clock of the hamsters stops these thyroid hormones from entering the hypothalamus – resulting in the re-growth of the reproductive system in time for the spring breeding season.

The researchers found that the three genes they studied were not being expressed significantly (in other words, they were turned off) in the hamsters who had been housed in short days for 32 weeks – the equivalent of normal hamsters in mid- to late winter. This means the hypothalamus in the hamsters would not be taking in thyroid hormones and their reproductive systems would begin to turn back on.

“These hamsters had lost their ability to respond to the signals of short days. This means that levels of thyroid hormones will drop in the hypothalamus and initiate the recovery of the reproductive system in mid-winter,” he said.

Overall, the studies show how the genes transthyretin, T4-binding globulin, and albumin allow the brain to regulate the levels of thyroid hormones in the hypothalamus, Prendergast said. This in turn regulates how the hamsters’ reproductive systems respond to changing seasons throughout the year.

“The availability of thyroid hormones influences the seasonal timekeeping mechanism,” he said.

Prendergast conducted the study with Bedrich Mosinger, a researcher at Ohio State’s Neurobiotechnology Center; Pappachan Kollattukudy, director of the Neurobiotechnology Center and professor of biochemistry; and Randy Nelson, professor of psychology.

Contact: Contact: Brian Prendergast, (614) 538-9540;
Brianp@psy.ohio-state.edu

Randy Nelson, (614) 247-6408; Rnelson@osu.edu