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Environmental Factor

May 2011

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Hormones and the stress response

By Robin Arnette
May 2011

Ron de Kloet, Ph.D.

NIEHS was honored to have Sir Ron de Kloet on campus. He was knighted in the Netherlands by the Order of the Dutch Lion (Orde van de Nederlandse Leeuw) in 2010. (Photo courtesy of Steve McCaw)

John Cidlowski, Ph.D.

Of all of the speaker's accolades, Cidlowski was most excited about de Kloet's academy professorship. He said of the appointment, "That's a very distinguished award where he receives a large sum of money, and is relieved of his academic and administrative duties and allowed to pursue his research interests." (Photo courtesy of Steve McCaw)

NIEHS/NTP Director Linda Birnbaum, Ph.D.

NIEHS/NTP Director Linda Birnbaum, Ph.D., took copious notes during the lecture. (Photo courtesy of Steve McCaw)

Ken Korach, Ph.D.

Laboratory of Reproductive and Developmental Toxicology Chief Ken Korach, Ph.D., asked a question regarding the disorganized cortisol pulse patterns in aged rats. (Photo courtesy of Steve McCaw)

According to NIEHS distinguished lecturer Ron de Kloet, Ph.D., everyday stressors induce specific physiological changes in the body. On April 12, de Kloet discussed those changes in a seminar titled "Resilience or Vulnerability to Environmental Challenge? A Question of Stress, Genes, and Balance." John Cidlowski, Ph.D., a principal investigator in the Laboratory of Signal Transduction, hosted the talk.

As an academy professor of the Royal Netherlands Academy of Sciences at Leiden University in the Netherlands, de Kloet( Exit NIEHS studies the role glucocorticoid receptors play in the initiation and termination of a stress response. He explained that glucocorticoid receptors, when bound to their proper ligand, activate or repress genes that control tissues and organ systems within the body. De Kloet began his talk with a definition of stress.

"A stressor is a stimulus that is perceived as a disturbance of homeostasis/integrity of the individual that evokes a response," he said. "There are physical and psychological stressors, with the most severe psychological stressor occurring when there is no information available to predict what the future brings, while evoking an uncertain anxious feeling."

De Kloet said he found a good example of a severe psychological stress during another seminar. He asked the audience which event had the greater impact, Japan's recent tsunami or the explosion at the Fukushima nuclear facility. Even though the tsunami produced greater devastation, 60 to 70 percent of the audience said Fukushima was worse. De Kloet said their response made sense because the majority of people are most afraid of threats that they can't define, predict, or control.

How the brain processes stress

De Kloet said that events that elicit strong emotion are remembered, and the brain's limbic system is responsible for processing this stressful information. Three major structures of the limbic system - the amygdala, hippocampus, and pre-frontal cortex - are highly interconnected, and disturbing their connectivity affects their function.

During stress, including the body's fight or flight response, de Kloet said that the autonomic nervous system becomes involved. It activates the hypothalamus-pituitary-adrenal axis, which produces hydrocortisone, a glucocorticoid hormone also known as cortisol. Normally, these elevated cortisol levels decrease after 90 minutes, but if a person fails to cope with the stress, cortisol concentrations remain high. He said prolonged exposure to cortisol may lead to several health disorders, such as heart disease, decreased bone density and muscle mass, and lowered immunity.

Hormone patterns are important for health

Cortisol is important during stress, but recent research in mice, examining the secretion pattern of cortisol during basal conditions, yielded an interesting finding. De Kloet and his team found that the hormone is released in a distinct hourly pulse pattern. The pulse peaks decreased during sleep or resting periods, but as the rats aged, the amplitude, frequency, and organization of the rhythm changed. In middle-aged rats, the pulses were less pronounced, while old rats displayed a disorganized pattern.

"In the case of aging, the hormone loses its ability to coordinate and synchronize the body-brain processes in order to be prepared for stressors," de Kloet said. "The basal hourly pulses are programmed, but stressors produce a spontaneous pulse."

De Kloet's experiment demonstrated that these pulses are important in determining how a person will deal with stress, and that the body needs the hourly exposure to cortisol to maintain its responsiveness and resilience. He added that in the case of depression, a mental disorder in which a person is unable to cope with a stressor, the pulse pattern differs from that of a non-depressed person. A depressed person has a large amplitude of cortisol levels when they should be low.

De Kloet added that genetic, societal, and environmental influences, particularly if experienced during early life, also affect how a person tolerates stress.

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