A cautionary note on oxytocin as a treatment for psychiatric disorders

Aug. 12, 2013 — The hormone oxytocin is known for its widespread effects on social and reproductive processes, and recent data from intranasal administration in humans has produced hope for its use as a therapeutic in autism, schizophrenia, and other disorders.However, this leap to human use is happening without previous animal studies of long-term oxytocin administration, and without knowledge of the neurobiological mechanisms involved in the behavioral findings.A new study now published in Biological Psychiatry indicates that the promising short-term effects often observed after a single dose of oxytocin may not translate to positive effects after long-term administration.This research was led by Dr. Karen Bales, Professor and Vice Chair of Psychology at the University of California. She and her colleagues examined the long-term effects of oxytocin treatment using the prairie vole, a small rodent that forms strong life-long pair bonds and is thus often used in studies of social behavior.Both male and female voles were treated with one of three dosages of intranasal oxytocin, administered daily from weaning through sexual maturity. During this time, the researchers observed and recorded the voles’ social interactions. They also conducted tests of social and anxiety-related behaviors in the adult voles, after the oxytocin treatment had finished, allowing them to measure any long-term effects.As expected, oxytocin treatment increased social behavior in male voles, similar to the effects repeatedly observed in humans. However, the long-term effects were concerning, with male voles showing deficits in their typical behaviors.”In this study, we showed that long-term exposure to oxytocin in adolescent male prairie voles led to disruption of social bond formation in these males as adults,” explained Bales. “Male prairie voles which received a dose similar to that being tested in humans, or even a lower dose, did not form pair-bonds normally with their pair-mate. Instead these males chose to associate with a strange female.”This important finding should suggest caution in the long-term use of intranasal oxytocin in developing humans.”The fact that long term treatment with oxytocin had the opposite impact of initial doses with the same substance suggests that special strategies will be needed if oxytocin is ever to become a long-term treatment for autism or schizophrenia,” said Dr. John Krystal, Editor of Biological Psychiatry.Bales agrees, and added, “In our continuing research program, we also have preliminary data suggesting that these treatments caused long-term changes in the oxytocin system. …

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Calcium and vitamin D help hormones help bones

June 26, 2013 — Should women take calcium and vitamin D supplements after menopause for bone health? Recommendations conflict, and opinions are strong. But now, an analysis from the major Women’s Health Initiative (WHI) trial throws weight on the supplement side — at least for women taking hormones after menopause. The analysis was published online today in Menopause, the journal of The North American Menopause Society.Among the nearly 30,000 postmenopausal women in the hormone trial, some 8,000 took supplemental calcium (1,000 mg/day) and vitamin D (400 mg/day), and some 8,000 took look-alike placebos. These women came from all the hormone groups in the study — those who took estrogen plus a progestogen (required for women with a uterus), those who took estrogen alone, and those who took the hormone look-alike placebos. The researchers looked at how the rates of hip fracture differed among women who took hormones and supplements, those who took hormones alone, and those who took neither.The supplements and hormones had a synergistic effect. Women using both therapies had much greater protection against hip fractures than with either therapy alone. Taking supplements alone wasn’t significantly better than taking no supplements and no hormones. The benefit of hormone therapy was strong in women who had a total calcium intake (supplements plus diet) greater than 1,200 mg/day. Similarly, the benefit was strong in women who had higher intakes of vitamin D, but the individual effect of each one could not be determined because the two supplements were given together.The effects translated into 11 hip fractures per 10,000 women per year among the women who took both hormones and supplements compared with 18 per 10,000 women per year among those who took hormones only, 25 per 10,000 women per year among those who took supplements alone, and 22 among those who got neither therapy.These results suggest, said the authors, that women taking postmenopausal hormone therapy should also take supplemental calcium and vitamin D. …

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Healthy, full-term babies use a different stress hormone than their mother

June 17, 2013 — A University of Calgary researcher has identified how a steroid hormone may indicate infant distress during labour and delivery. The study, published by PLOS ONE this month, suggests that a full-term, healthy baby preferentially secretes a different stress hormone than its mother does. That stress hormone, corticosterone, has not been previously studied in human development.”Fetal corticosterone, which is related to cortisol, could serve as a biomarker of fetal stress,” says study lead author Katherine Wynne-Edwards, PhD, Jack Manns Professor of Comparative Endocrinology. Wynne-Edwards worked with clinical obstetrician/gynecologist Heather Edwards on the study.”Since cortisol is found in much higher concentrations than corticosterone, it has received greater attention as an indicator of stress in both mothers and newborns.”In this study, investigators compared the concentrations of hormones in the umbilical cord to assess the hormones added to the circulation by the baby. Corticosterone increased during labor and delivery at a significantly greater rate compared to cortisol, although overall cortisol levels were still higher. As fetal stress increased, so did corticosterone concentrations.Investigators analyzed umbilical cord blood samples from 265 healthy deliveries. Corticosterone concentrations varied according to the delivery — compared to infants delivered by Caesarian section, vaginally delivered infants synthesized greater concentrations of corticosterone. When Caesarian delivery occurred because the baby’s head was too large to pass through the birth canal, which was expected to be a stressor on the baby, the highest corticosterone concentrations were seen. Meanwhile, intervention to strengthen maternal contractions did not increase corticosterone concentrations.”Newborn corticosterone synthesis might be the basis for a signal to the mother that the baby is in distress, and might also indicate that a previously unsuspected developmental transition from preferential corticosterone synthesis to preferential cortisol synthesis occurs in early life,” Wynne-Edwards said. “If so, then corticosterone might be an important biomarker of adrenal function in premature infants that is not yet studied or understood.”Wynne-Edwards presented her findings at the Endocrine Society Annual Meeting in San Francisco on June 15, 2013. …

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Red wine could mask testosterone levels, experts warn

Jan. 7, 2013 — Red wine could give athletes and players a boost in the sports arena by increasing the amount of performance-enhancing hormone testosterone in their bodies, according to researchers from London’s Kingston University.

However not only could the beverage help them to trophy success, it could also allow them to beat anti-doping tests. A team led by Professor Declan Naughton, from the University’s School of Life Sciences, found that red wine might reduce the amount of testosterone excreted by the body, which could distort the findings of drug tests taken from urine samples.

Testosterone is a naturally-occurring steroid hormone present in both men and women. It can increase muscle mass, boost stamina and speed up recovery. Sportspeople, however, are prohibited from taking it, or a synthetic version of it, to try to gain a competitive edge.

Although red wine is not a banned substance away from the sports field, Professor Naughton’s team has referred its findings to the World Anti-Doping Agency because of the newly-discovered side effect of potential change to the amount of testosterone in the body.

“Previous research has shown the effect over-the-counter anti-inflammatory drugs can have on enzymes,” Professor Naughton explained. “Since many of these drugs are derived from plants, we decided to look at the effect particular foods and beverages can have on enzymes involved in testosterone excretion. We chose green tea and then red wine because both have a huge variety of natural molecules and we wanted to see if they affected the amount of testosterone excreted in urine.”

The team found that a compound in red wine, known as quercetin, partially blocked the action of an enzyme called UGT2B17, which looks for testosterone and then sends a message to the kidneys to excrete it.

Professor Naughton stressed that the research had so far been conducted in test tube experiments and had yet to be trialled on humans. “A full clinical study would be needed to determine the effects on people but, if the same results were found, it would confirm that compounds in red wine can reduce the amount of testosterone in urine and give a boost to testosterone levels,” he explained.

The effect of red wine on an individual would vary because of factors such as weight, fitness, health and diet, making it hard to estimate how much was needed to improve performance, Professor Naughton said.

Teetotallers are not exempt from the effects. In fact, the alcohol content of red wine has very little impact because non-alcoholic molecules are responsible for inhibiting testosterone excretion.

The team also found the results were the same for red wine extract in supplement form. The active compounds such as quercetin are found in many foodstuffs as well as supplements.

The findings have been published in leading international journal Nutrition. The research follows an earlier study from Professor Naughton’s team which showed that green and white tea could also inhibit testosterone excretion.

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Herbal treatments for postmenopausal symptoms may be recommended as an alternative to hormone replacement therapy

Jan. 10, 2013 — Herbal and complementary medicines could be recommended as an alternative to hormone replacement therapy (HRT) for treating postmenopausal symptoms says a new review published January 11 in The Obstetrician and Gynaecologist (TOG).

The review outlines the advantages and limitations of both pharmacological and herbal and complementary treatments for women with postmenopausal symptoms.

The menopause is defined as the time after a woman’s menstrual periods have ceased (12 months after a woman’s final menstrual period). It is associated with an estrogen deficiency and can cause an increase in vasomotor symptoms (hot flushes), genitourinary symptoms (vaginal dryness, sexual dysfunction, frequent urinary tract infections, urinary incontinence), and musculoskeletal symptoms (joint pain) as well as sleep and mood disturbance.

One of the most common menopausal symptoms is hot flushes; approximately two-thirds of postmenopausal women will experience them, and 20% of women can experience them for up to 15 years, states the review.

Estrogen deficiency can also lead to longer-term health issues such as cardiovascular disease and osteoporosis. While pharmacological agents are available to treat postmenopausal symptoms, many non-pharmacological treatment options are also available.

HRT is the most effective treatment of hot flushes, improving symptoms in 80 — 90% of women, says the review. However, the author notes that there are possible health risks associated with HRT, such as links to breast cancer, blood clots, stroke, and cardiovascular problems.

Due to these possible risks, other treatment options may be equally effective, such as behaviour modification and herbal and complimentary medicines, says the author.

The review states that as many as 50 — 75% of postmenopausal women use herbal options to treat hot flushes, and of the complimentary therapies, soy, red clover and black cohosh have been the most investigated.

Soy is the most common plant containing estrogen, found naturally in food and supplements. Previous research has shown a reduction in hot flush symptoms with soy ranging from 20 — 55%. Red clover, a legume also containing estrogen, and black cohosh, a plant originating from the eastern United States and Canada, have also been reported to ease postmenopausal symptoms.

The author of the review recommends these herbal treatments as there are no significant adverse side effects associated with them, as long as they are used in women who do not have a personal history of breast cancer, are not at high risk for breast cancer, and are not taking tamoxifen. However, the review notes that herbal medicines are not regulated in many countries, and therefore the contents of a given product may vary from sample to sample.

Iris Tong, Director of Women’s Primary Care at the Women’s Medicine Collaborative, The Warren Alpert Medical School of Brown University, Rhode Island, and author of the review said:

“Up to 75% of women use herbal and complimentary medicines to treat their postmenopausal symptoms. Therefore, it is vitally important for healthcare providers to be aware of and informed about the non-pharmacological therapies available for women who are experiencing postmenopausal symptoms and who are looking for an alternative to HRT.”

TOG‘s Editor -in-Chief, Jason Waugh said:

“Postmenopausal symptoms can be very distressing and it is important to review the advantages and limitations of the non-pharmacological treatments available as well as the pharmacological ones. Even simple behaviour modification can make a difference to postmenopausal symptoms, including keeping the room temperature cool, wearing layered clothing, relaxation techniques and smoking cessation.”

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KISS ME DEADLY proteins may help improve crop yields

May 27, 2013 — Dartmouth College researchers have identified a new regulator for plant hormone signaling — the KISS ME DEADLY family of proteins (KMDs) – that may help to improve production of fruits, vegetables and grains.


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The study’s results will be published the week of May 27 in the journal Proceedings of the National Academy of Sciences.

Professor G. Eric Schaller, the paper’s senior author, studies the molecular mechanisms by which a plant recognizes a hormone and then responds to it. Among the hormones he studies are “anti-aging” cytokinins, which play critical roles in regulating plant growth and development, including stimulating yield, greening, branching, metabolism and cell division. Cytokinins are used in agriculture for multiple purposes, from crops to golf course greens.

In their PNAS paper, the researchers identify KMDs as a new regulator for cytokinin signaling. To regulate plant growth, plants need to perceive cytokinins and convert this information into changes in gene expression. The KMDs target a key group of cytokinin-regulated transcription factors for destruction, thereby regulating the gene expression changes that occur in response to cytokinin. In other words, increases in KMD levels result in a decreased cytokinin response (or less crop growth), while decreases in KMD levels result in a heightened cytokinin response (or greater crop growth).

The results suggest that KMDs represent a natural means by which plants can regulate the cytokinin response and may serve as a method to help regulate agriculturally important cytokinin responses.

“We expect that a better understanding of cytokinin activity and KMDs could lead to improved agricultural productivity,” said Schaller.

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The above story is reprinted from materials provided by Dartmouth College, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Hyo Jung Kim, Yi-Hsuan Chiang, Joseph J. Kieber, and G. Eric Schaller. SCFKMD controls cytokinin signaling by regulating the degradation of type-B response regulators. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1300403110

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