Friday, December 29, 2006

 

Sex Ends as Seasons Shift and Kisspeptin Levels Plummet

A hormone implicated in the onset of human puberty also appears to control reproductive activity in seasonally breeding rodents, report Indiana University Bloomington and University of California at Berkeley scientists in the March 2007 issue of Endocrinology.

The researchers present evidence that kisspeptin*, a recently discovered neuropeptide encoded by the KiSS-1 gene, mediates the decline of male Siberian hamsters' libido and reproduction as winter approaches and daylight hours wane.

'Ours isn't the first study to link the peptide to reproduction, but it is the first to connect kisspeptin to how animals interpret seasonal cues, including day length,' said IUB biologist Gregory Demas**. 'Kisspeptin likely plays an integral role in coordinating seasonal reproduction in a wide range of animals.'

Kisspeptin joins a select few proteins believed to act as switches that connect environmental changes to a physiological response.

"This peptide is poised to act as an integrator of environmental information to allow for the optimal neuroendocrine control of reproduction in vertebrates, including humans," said UC Berkeley neuroscientist Lance Kriegsfeld. "In humans and other species, if the environment is not satisfactory, sex drive will decline; kisspeptin is likely part of the pathway responsible for this regulation."

The scientists divided a population of male Siberian hamsters (Phodopus sungorus) into treatment groups: those housed in long, summer-like photoperiods and those in short, winter-like photoperiods. In a separate experiment hamsters were also treated with exogenous injections of kisspeptin after eight weeks of either short- or long-day photoperiod exposure. At the conclusion of the experimental period, scientists analyzed the hamsters' reproductive system status, blood levels of reproductive hormones, as well as the number of kisspeptin-expressing cells in the brain.

They found hamsters in wintry conditions experienced marked reductions of kisspeptin in a critical brain region important for regulating reproduction and sex behavior compared to hamsters in simulated summer conditions.

Winter hamsters, however, were just as responsive to kisspeptin, elevating a key hormone - luteinizing hormone - as much as hamsters in simulated summers. This finding indicates the ability of this hormone to turn on the reproductive switch even in the presence of cues signaling a winter, non-breeding environment.

"What is really striking is the disappearance of kisspeptin in animals experiencing winter-like days, yet the ability to respond to kisspeptin when we provide it," said Timothy Greives, lead author of the study. "These data show that the disappearance of kisspeptin in the brain is likely critical in turning off reproduction during winter."

Recent research by scientists in the U.K. and France have shown human kisspeptin triggers the release of gonadotropin-releasing hormone and luteinizing hormone, both of which are important to puberty and other sex-related functions.

"Studies in humans have shown that individuals with deficits in the receptor for kisspeptin have severe reproductive impairments," Demas said.

Kisspeptin's role in seasonal human reproduction, however, is unknown - that is, if it even has one. It is interesting to note the CDC reports fertility rates in the United States decrease rapidly in autumn. The phenomenon is particularly clear-cut among Caucasians, believed to have originated in more temperate climes.

KiSS-1 and kisspeptin were not named whimsically. They were originally associated with metastatic tumor suppression (the SS in KiSS-1 stands for "suppressor sequence"). The subsequent connection of KiSS-1 and kisspeptin to reproductive function was entirely fortuitous.

IUB biologist Ellen Ketterson and graduate student Melissa-Ann Scotti, and UC Berkeley graduate student Alex Mason and undergraduate student Jacob Levine also contributed to the research. It was funded by grants from Indiana University and UC Berkeley.

Source: Indiana University PR December 28, 2006

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Based on the Endochrinology paper:

Environmental Control of Kisspeptin: Implications for Seasonal Reproduction

By Timothy J. Greives, Alex O. Mason, Melissa-Ann L. Scotti, Jacob Levine, Ellen D. Ketterson, Lance J. Kriegsfeld, and Gregory E. Demas

Endocrinology Vol. 148, No. 3 1158-1166
Endocrinology, doi:10.1210/en.2006-1249

Abstract

The KiSS-1 gene encodes the peptide hormone kisspeptin, which acts as a principal positive regulator of the reproductive axis by directly stimulating GnRH neuron activity. To gain insight into a potential role for kisspeptin in integrating and relaying reproductively-relevant stimuli to the GnRH system, we investigated changes in kisspeptin peptide expression associated with photoperiodic changes in reproductive state, as well as pituitary and gonadal responses to peripheral kisspeptin injections. Seasonally breeding rodents undergo pronounced fluctuations in reproductive state in response to changing day lengths. In common with other rodent species, a majority of male Siberian hamsters (Phodopus sungorus) exhibit reproductive decline following exposure to short day lengths. A subset of individuals fails to respond to day length information, however, and maintains their reproductive function. We exploited these individual differences to examine whether kisspeptin may act at the interface between external stimuli and the reproductive system. Following extended exposure to short days, animals with a quiescent reproductive axis displayed a marked reduction in kisspeptin cell labeling in the AVPV, but robust kisspeptin-ir staining in the ARC. In contrast, animals with functional reproductive systems displayed high numbers of kisspeptin-ir neurons in the AVPV, but a paucity of expression in the ARC. Kisspeptin injections significantly elevated LH over pre-injection levels regardless of photoperiod or reproductive state. Collectively, these findings suggest an important role for kisspeptin in coordinating and relaying environmentally relevant information to the reproductive axis, as well as a role for this peptide in regulating seasonal changes in reproductive function.

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*Info on Kisspeptin from the Observer (July '05):

It is sealed with a kiss. Researchers have found that a protein called kisspeptin triggers the cascade of biochemical changes that leads to puberty and turns children into hormonally challenged adolescents.

The discovery raises hopes of understanding one of human biology's fundamental processes, when a young person's body is propelled towards sexual maturity, turning a normal, happy child into a sulking, spotty teenager.

More importantly, the finding could lead to the development of drugs to block the premature onset of sexuality in very young children.

The discovery also raises prospects of developing new treatments for breast and prostate cancer. These tumours are nourished by sex hormones that are in turn controlled by kisspeptin.

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**Info from Demas Lab:

The primary focus of our laboratory is in the general area of "ecological physiology". Specifically, we study of the interactions among the nervous, endocrine and immune systems and behavior in a variety of ecologically relevant environmental contexts. For example, many non-tropical organisms experience pronounced fluctuations in environmental conditions (e.g., day length, ambient temperature, food availability, social interactions) across the seasons of the year. Consequently, individuals of a wide range of species have evolved specific adaptive mechanisms to cope with seasonal fluctuations in the environment. These adaptations may be physiological (e.g., changes in energy balance, reproductive function or immunity) or behavioral (e.g., changes in foraging, migration, aggression or social behavior). The broad goal of our research is to identity the environmental and social factors contributing to seasonal changes in specific physiological and behavioral responses and to determine the neural, endocrine and immune mechanisms underlying these changes. Although this research focuses primarily on rodent species (e.g., Siberian hamsters, deer mice, voles), we also address these questions in amphibian and avian species.

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