Posts tagged sex hormones
Articles and news from the latest research reports.
Estrogen receptor expression may help explain why more males have autism
The same sex hormone that helps protect females from stroke may also reduce their risk of autism, scientists say.
In the first look at a potential role of the female sex hormone in autism, researchers at the Medical College of Georgia at Georgia Regents University have found expression of estrogen receptor beta – which enables estrogen’s potent brain protection – is significantly decreased in autistic brains. The receptor also plays a role in locomotion as well as behavior, including anxiety, depression, memory, and learning.
"If you ask any psychiatrist seeing patients with autistic behavior their most striking observation from the clinic, they will say there are more males compared to females," said Dr. Anilkumar Pillai, MCG neuroscientist and corresponding author of the study in Molecular Autism.
Estrogen is known to help protect premenopausal women from maladies such as stroke and impaired cognition. Exposure to high levels of the male hormone testosterone during early development has been linked to autism, which is five times more common in males than females.
The new findings of reduced expression of estrogen receptor beta as well as that of an enzyme that converts testosterone to estrogen could help explain the high testosterone levels in autistic individuals and higher autism rates in males, Pillai said.
It was the 5-to-1 male-to-female ratio along with the testosterone hypothesis that led Pillai and his colleagues to pursue whether estrogen might help explain the significant gender disparity and possibly point toward a new treatment.
"The testosterone hypothesis is already there, but nobody had investigated whether it had anything to do with the female hormone in the brain," Pillai said. "Estrogen is known to be neuroprotective, but nobody has looked at whether its function is impaired in the brain of individuals with autism. We found that the children with autism didn’t have sufficient estrogen receptor beta expression to mediate the protective benefits of estrogen."
Comparing the brains of 13 children with and 13 children without autism spectrum disorder, the researchers found a 35 percent decrease in estrogen receptor beta expression as well as a 38 percent reduction in the amount of aromatase, the enzyme that converts testosterone to estrogen.
Levels of estrogen receptor beta proteins, the active molecules that result from gene expression and enable functions like brain protection, were similarly low. There was no discernable change in expression levels of estrogen receptor alpha, which mediates sexual behavior.
The study focused on the brain’s prefrontal cortex, which is involved in social behavior and cognition. Brain tissue from both autistic and healthy subjects was obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Brain and Tissue Bank for Developmental Disorders at the University of Maryland. The children died at an average age of 11 from drowning, other accidents, or suicide. All the brain tissue was from male children except for one control.
While much work remains, estrogen receptor beta agonists, which are already known to improve brain plasticity and memory in animals, might one day help reverse autism’s behavioral deficits, such as reclusiveness and repetitive behavior, Pillai said.
The scientists already are moving to animal studies to see what happens when they reduce estrogen receptor beta expression in mice. They also plan to give an estrogen receptor beta agonist – which should increase receptor function – to a mouse with generalized inflammation and signs of autism to see if it mitigates those signs. Inflammation is a factor in many diseases of the brain and body, and estrogen receptor beta agonists already are in clinical trials for schizophrenia
Larger, follow-up studies should also include comparing expression of testosterone receptor levels in healthy and autistic children, Pillai said. MCG scientists also want to know more about why the reduced beta receptor expression occurs.
Studies published in the journal Molecular Psychiatry earlier this year by scientists at the University of Cambridge and Denmark’s Statens Serum Institute showed that male children who develop autism were exposed to higher levels of steroid hormones, including testosterone and progesterone, during development than their healthy peers.
The incidence of autism has increased about 30 percent in the past two years in the United States, to the current rate of about 1 in 68 children, according to the Centers for Disease Control and Prevention. Most children are diagnosed at about age 4, although the disorder can be diagnosed by about age 2, according to the CDC. Diagnosis is made through extensive behavioral and psychological testing.
(Source: eurekalert.org)
Understanding parallels of human and animal parenting can benefit generations to come
Strong evidence now shows that human and animal parenting share many nervous system mechanisms. This is the conclusion of Yerkes National Primate Research Center researchers Larry Young, PhD, and James Rilling, PhD, in their review article about the biology of mammalian parenting, published in this week’s issue of Science. Better understanding this biology could lead to improved social development, benefitting generations of humans and animals to come.
In their article, Young and Rilling review the biological mechanisms governing a shift in mammals’ parental motivation that begins with aversion and transforms into irresistible attraction after giving birth. They say the same molecules that prepare the uterus for pregnancy, stimulate milk production and initiate labor also activate specific neural pathways to motivate parents to nurture, bond with and protect their offspring.
According to Young, “We have learned a tremendous amount about the specific hormonal and brain mechanisms regulating parental behavior and how parental nurturing influences the development of the offspring brain by using animal models, and many of these same mechanisms influence human parenting behavior as well.”
Young is division chief of Behavioral Neuroscience and Psychiatric Disorders at the Yerkes Research Center, director of the Center for Translational Social Neuroscience at Emory, a William P. Timmie professor in the Department of Psychiatry at Emory’s School of Medicine and author of The Chemistry Between Us: Love, Sex and the Science of Attraction, which also summarizes the parallels between brain mechanisms regulating sexual and parenting behaviors in animals and humans.
Rilling, who is a Yerkes researcher and an associate professor in Emory’s Department of Anthropology, adds, “The human brain has mechanisms in place to support parent-child bonding, and when functioning properly, these mechanisms facilitate the development of secure attachment and sound mental health that is transmitted across generations.”
The researchers divided their review into nine categories, including neural correlates of human parental care, two specific to parenting and oxytocin, two focused specifically on paternal caregiving by fathers and two related to the effect of parenting on social development. Examples within these categories include that the frustration inconsolable infant crying induces is a risk factor for infant abuse, highlighting the importance of emotion regulation for sensitive parenting; that oxytocin affects maternal motivation and paternal behaviors essential for nurturing, bonding and defending the offspring; that testosterone may interfere with parenting effort; and that variation in parental nurturing can affect brain development, thus affecting future social behaviors.
“With this comprehensive review, we can see nervous system correlations across species that result in positive and negative parental care,” says Young. “This information is critical to further studying social development in order to facilitate positive parental behaviors that will benefit generations to come,” he continues.
Study reveals one reason brain tumors are more common in men
New research at Washington University School of Medicine in St. Louis helps explain why brain tumors occur more often in males and frequently are more harmful than similar tumors in females. For example, glioblastomas, the most common malignant brain tumors, are diagnosed twice as often in males, who suffer greater cognitive impairments than females and do not survive as long.
The researchers found that retinoblastoma protein (RB), a protein known to reduce cancer risk, is significantly less active in male brain cells than in female brain cells.
The study appears Aug. 1 in The Journal of Clinical Investigation.
“This is the first time anyone ever has identified a sex-linked difference that affects tumor risk and is intrinsic to cells, and that’s very exciting,” said senior author Joshua Rubin, MD, PhD. “These results suggest we need to go back and look at multiple pathways linked to cancer, checking for sex differences. Sex-based distinctions at the level of the cell may not only influence cancer risk but also the effectiveness of treatments.”
Rubin noted that RB is the target of drugs now being evaluated in clinical trials. Trial organizers hope the drugs trigger the protein’s anti-tumor effects and help cancer patients survive longer.
“In clinical trials, we typically examine data from male and female patients together, and that could be masking positive or negative responses that are limited to one sex,” said Rubin, who is an associate professor of pediatrics, neurology and anatomy and neurobiology. “At the very least, we should think about analyzing data for males and females separately in clinical trials.”
Scientists have identified many sex-linked diseases that either occur at different rates in males and females or cause different symptoms based on sex. These distinctions often are linked to sex hormones, which create and maintain many but not all of the biological differences between the sexes.
However, Rubin and his colleagues knew that sex hormones could not account for the differences in brain tumor risk.
“Male brain tumor risk remains higher throughout life despite major age-linked shifts in sex hormone production in males and females,” he said. “If the sex hormones were causing this effect, we’d see major changes in the relative rates of brain tumors in males and females at puberty. But they don’t happen then or later in life when menopause changes female sex hormone production.”
Rubin used a cell model of glioblastoma to prove it is easier to make male brain cells become tumors. After a series of genetic alterations and exposure to a growth factor, male brain cells became cancerous faster and more often than female brain cells.
In experiments designed to identify the reasons for the differences in the male and female cells, the team evaluated three genes to see if they were naturally less active in male brain cells. The genes they studied — neurofibromin, p53 and RB — normally suppress cell division and cell survival. They are mutated and disabled in many cancers.
The scientists found RB was more likely to be inactivated in male brain cells than in female brain cells. When they disabled the RB protein in female brain cells, the cells were equally susceptible to becoming cancers.
“There are other types of tumors that occur at different rates based on sex, such as some liver cancers, which occur more often in males,” Rubin said. “Knowing more about why cancer rates differ between males and females will help us understand basic mechanisms in cancer, seek more effective therapies and perform more informative clinical trials.”
(Source: news.wustl.edu)
Short circuit in molecular switch intensifies pain
Pain functions as an important alarm signal. It alerts us to potential bodily harm – a hot or sharp object, for example – and motivates us to withdraw from damaging situations. At the cellular level, pain involves the stimulation of a network of pain nerves spread through the skin, mucosa and bodily organs.
Embedded in the cell wall surrounding these nerves are ion channels. These tiny, microscopic pathways respond to stimuli such as extreme cold or heat, mechanical pressure or harmful chemicals. When ion channels open, an electrical signal is created, transmitted to the brain, and interpreted as pain.
In previous research, the team of KU Leuven researchers led by Professor Thomas Voets (Laboratory of Ion Channel Research) and Professor Joris Vriens (Laboratory of Obstetrics and Experimental Gynaecology) discovered that a particular ion channel – TRPM3 – acts as a molecular fire detector: the ion channel detects heat and the hormone pregnenolone sulfate, a precursor to the sex hormones estrogen and testosterone and a trigger for pain and inflammation. In the present study, the researchers were looking for TRPM3 inhibitors that could potentially be used as painkillers.
Short circuit
Surprisingly, their results show that a number of drugs meant as painkillers actually increased pain in mice tested in the study, says Professor Voets: “Normally, when the ion channel is closed, no electrical signal is sent to the brain and therefore no pain is detected. But we found that pain can indeed occur despite a closed ion channel. How? A short circuit in the ion channel. When short-circuiting occurs, the electrical signal effected by a stimulus does not follow the normal pathway through the central pore of the ion channel. Instead, it navigates an alternative path through the surrounding material. This ‘electrical leak’ activates the pain nerves, thus increasing the sensation of pain. This may explain the pain-enhancing side effects of some drugs – such as clotrimazole, a common remedy for yeast infections that often causes unpleasant side effects such as irritation and burning sensations.”
“It is striking that short circuits in the ion channel only occur at high hormone levels. This could explain why some patients experience these side effects while others do not,” says Professor Voets. The researchers hope this new knowledge about TRPM3-dependent pain will contribute to the development of new painkillers with fewer painful side effects.
Brain Anatomy of Dyslexia Is Not the Same in Men and Women, Boys and Girls
Using MRI, neuroscientists at Georgetown University Medical Center found significant differences in brain anatomy when comparing men and women with dyslexia to their non-dyslexic control groups, suggesting that the disorder may have a different brain-based manifestation based on sex.
Their study, investigating dyslexia in both males and females,is the first to directly compare brain anatomy of females with and without dyslexia (in children and adults). Their findings were published online in the journal Brain Structure and Function.
Because dyslexia is two to three times more prevalent in males compared with females, “females have been overlooked,” says senior author Guinevere Eden, PhD, director for the Center for the Study of Learning and past-president of the International Dyslexia Association.
“It has been assumed that results of studies conducted in men are generalizable to both sexes. But our research suggests that researchers need to tackle dyslexia in each sex separately to address questions about its origin and potentially, treatment,” Eden says.
Previous work outside of dyslexia demonstrates that male and female brains are different in general, adds the study’s lead author, Tanya Evans, PhD.
“There is sex-specific variance in brain anatomy and females tend to use both hemispheres for language tasks, while males just the left,” Evans says. “It is also known that sex hormones are related to brain anatomy and that female sex hormones such as estrogen can be protective after brain injury, suggesting another avenue that might lead to the sex-specific findings reported in this study.”
The study of 118 participants compared the brain structure of people with dyslexia to those without and was conducted separately in men, women, boys and girls. In the males, less gray matter volume is found in dyslexics in areas of the brain used to process language, consistent with previous work. In the females, less gray matter volume is found in dyslexics in areas involved in sensory and motor processing.
The results have important implications for understanding the origin of dyslexia and the relationship between language and sensory processing, says Evans.
Scientists unpack testosterone’s role in schizophrenia
Testosterone may trigger a brain chemical process linked to schizophrenia but the same sex hormone can also improve cognitive thinking skills in men with the disorder, two new studies show.
Scientists have long suspected testosterone plays an important role in schizophrenia, which affects more men than women. Men are also more likely to develop psychosis in adolescence, previous research has shown.
A new study on lab rodents by researchers from Neuroscience Research Australia analysed the impact increased testosterone had on levels of dopamine, a brain chemical linked to psychotic symptoms of schizophrenia.
The researchers found that testosterone boosted dopamine sensitivity in adolescent male rodents.
“From these rodent studies, we hypothesise that adolescent increases in circulating testosterone may be a driver of increased dopamine activity in the brains of individuals susceptible to psychosis and schizophrenia,” said senior Neuroscience Research Australia researcher and author of the study, Dr Tertia Purves-Tyson, who is presenting her work at the International Congress on Schizophrenia Research in Florida this week.
Dr Philip Mitchell, Scientia Professor and Head of the School of Psychiatry at the University of NSW, said the research was very interesting.
“The relationship between sex steroids, such as testosterone, and psychiatric disorders has long intrigued researchers. For example, we have known for many years that schizophrenia presents earlier in males than females, but the biological mechanism for this has been poorly understood,” said Dr Mitchell, who was not involved in the study.
“The rodent study by Professor Shannon Weickert from the School of Psychiatry at UNSW and NeuRA is therefore of particular interest. This study suggests an important interplay between circulating testosterone levels and the brain’s sensitivity to dopamine – a neurochemical which has been long implicated in the cause of schizophrenia,” said Dr Mitchell.
“This study suggests that it is the interplay between testosterone and dopamine which is critical. This is an important observation which may very well throw an important light on solving the puzzle of the biological causes of schizophrenia.”
Cognitive thinking
A separate study by Dr Thomas Weickert at Neuroscience Research Australia examined the role testosterone plays in the cognitive thinking skills of men with schizophrenia.
The researchers examined testosterone levels in a group of 29 chronically ill men with schizophrenia or schizoaffective disorder, and a control group of 20 healthy men and asked both groups to take a series of cognition tests.
“Circulating testosterone levels significantly predicted performance on verbal memory, processing speed, and working memory in men with schizophrenia … such that increased normal levels of testosterone were beneficial to thought processing in men with schizophrenia but circulating sex steroid levels did not appear to be related to cognitive function in healthy men,” the researchers reported.
“The results suggest that circulating sex steroids may influence thought processes in men with schizophrenia.”
Dr Melanie McDowall, a researcher at the University of Adelaide’s Robinson Institute, said the study added to a large body of evidence demonstrating a link between testosterone and schizophrenia.
“This is not surprising, given the link between testosterone and dopamine,” she said, adding that symptoms of schizophrenia predominantly began after puberty.
“However, as with most endocrine and mental illnesses, schizophrenia is multifaceted (genetic, environmental etc.), hence this may not be the be all and end.”
(Source: theconversation.com)