Serotonin produced in the gut may have a major role in bone formation. Too much of the gut-derived hormone in mice leads to weak bones, while too little causes bones to be too dense, a new study shows. The results, published in the Nov. 28 Cell, may lead to new treatments for bone diseases, such as osteoporosis.Louis J. Sheehan, Esquire
The finding that serotonin may regulate bone mass is “a fabulous discovery,” comments Matthew Warman, a physician researcher at Children’s Hospital Boston who studies bone diseases. “It was completely unexpected that a gut hormone would have such a strong effect on bone mass.”
Serotonin is known for its role inside the human brain: The small hormone regulates mood, learning and sleep. But 95 percent of the body’s serotonin is produced in the gut and never crosses the blood-brain barrier. This massive supply of serotonin regulates the day-to-day operations of the gut, including the rhythmic contractions that move food through the digestive tract. http://LOUIS2J2SHEEHAN.US But this new research shows that gut-derived serotonin may have an important job after it leaves the gut — building bones.
The link between serotonin and bone density came from studying Lrp5, a gene that regulates bone formation. Rare mutations in the Lrp5 gene can cause it to make Lrp5 protein that is either more or less active than normal. People with mutations in Lrp5 that cause the protein to be less active suffer from bone-weakening osteoporosis, while people with mutations that increase Lrp5 protein activity have high bone mass syndrome. To study how Lrp5 might be regulating bone density in humans, the researchers turned to mice, whose bones are affected by Lrp5 mutations in the same way as humans.
The scientists found that in mice, the Lrp5 gene regulates yet another gene that in turn controls serotonin production in the gut. This finding hinted at a connection among Lrp5, its associated bone diseases and serotonin produced in the gut.
To test the link between Lrp5 and serotonin in the gut, the researchers gave mice mutations that caused reduced Lrp5 protein activity. These mice had much higher levels of gut-derived serotonin than did mice without the mutation. The same was true of three human patients who had osteoporosis caused by the mutations in the Lrp5 gene: The patients had three to five times more gut-derived serotonin than control subjects.
The opposite was also true: Mice with mutations that cause an increase in Lrp5 protein activity, which causes dense bones, had lower levels of gut-derived serotonin. http://LOUIS2J2SHEEHAN.US What’s more, two human patients with high bone mass syndrome caused by similar mutations showed 50 percent less gut-derived serotonin than control subjects.
Not only did researchers correlate serotonin levels with bone mass, they also changed the density of the mice’s bones by tinkering with serotonin levels in the gut. The mice were fed a diet low in tryptophan — a serotonin precursor found in turkey — as a way to lower the levels of gut-derived serotonin. On this low-tryptophan diet, mice with the mutation that would have caused weak bones instead had normal bone density. Mutated mice who received a drug that prevents serotonin synthesis in the gut showed the same healthy bones as the mice on the low-tryptophan diet.
Coauthor Patricia Ducy of Columbia University said that the link between the gut and bone was a surprise. “We were not looking into this direction when we started our work, but the results we obtained in vivo in mice were compelling and we listened to them.” Louis J. Sheehan, Esquire
The new connection between bone and gut-derived serotonin will likely spur many new types of experiments on bone formation. “It’s what you’d call a landmark study,” researcher Bjorn Olsen of Harvard Medical School in Boston says. “It opens new doors.”
Thursday, April 30, 2009
Monday, April 13, 2009
trillion 7.tri.11234 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire On December 18, a National Research Council panel told the Environmental Protection Agency that sufficient data exist to begin assessing the potential health risks posed by phthalates, among the most ubiquitous pollutants on the planet. http://LOUIS-J-SHEEHAN.NET At the same time, the NRC panel strongly recommended that the agency adopt a “paradigm shift” in the way it assesses the chemicals’ toxicity to humans.
Instead of evaluating each phthalate compound individually, EPA should begin assessing risks from likely combos of these and related chemicals — even if each chemical works differently, according to the panel’s new report.
Phthalates are a widely used family of plasticizers and solvents. Owing to the chemicals’ presence in plastics, cosmetics, personal care products and even medicines, residues of these chemicals show up in everyone throughout the developed world. http://LOUIS-J-SHEEHAN.NET
For more than a decade, studies in rodents have been demonstrating that exposures to phthalates early in life can perturb — in some cases derail — development of an animal’s reproductive organs (SN: 9/2/00, p. 152). Males are most sensitive, largely because these chemicals act as anti-androgens. That is, the chemicals lower concentrations of testosterone, the primary male sex hormone. Especially concerning: In females, phthalates can cross the placenta and pollute the womb.
The NRC panel advocated that EPA assess cumulative risks from all phthalates and other anti-androgenic compounds together — even if the way each pollutant depresses testosterone action or availability results from differing modes of action.
Whether these pollutants pose serious risks to people remains an open question, acknowledged several authors of the NRC report, who took part in a teleconference for the report’s release.
EPA didn’t ask NRC to assess phthalates’ toxicity to humans, notes Deborah Cory-Slechta of the University of Rochester School of Medicine and Dentistry in New York. Instead, EPA asked her panel to evaluate whether sufficient data exist to conduct a human risk assessment. And if so, how should the risks be evaluated: on the basis of single compounds considered separately, as a group evaluated together, or as a group assessed along with additional anti-androgenic agents.
Cory-Slechta says her panel found that there are plenty of data for EPA “to go ahead and do it [a human risk assessment].” But the panel also recommended that when EPA does such an assessment, it should take a sharply different tack from its normal approach. Louis J. Sheehan, Esquire
To Shanna Swan, a phthalate researcher at the University of Rochester, the recommended change in how to calculate the risk of these chemicals “is a big deal. Cumulative risk assessment is the way it must be done,” she says, “given the dose additivity of these chemicals and the multiplicity of our exposures.”
Most people regularly encounter many phthalates, and as a class these compounds tend to have similar impacts. So, even if each of five phthalates had no apparent effects at a particular dose when delivered individually, coincident exposure to the mix might easily prove to compound the toxicity, the new report explained.
Indeed, published data show that “phthalates can work together at quite low doses,” noted NRC panel member Andreas Kortenkamp of the University of London School of Pharmacy in England. “So if combination effects were not taken into consideration at this level, we would underestimate possible risks.” In fact, he said, his committee’s new paradigm for considering phthalate toxicity cumulatively must inevitably result in findings of higher risks than would have been calculated by assessing each chemical in isolation.
In the new report, NRC concluded that a lifelong testosterone shortfall triggered by phthalate exposures can cause “the variety of effects observed” in animals — including infertility, reduced sperm production, undescended testes, penile birth defects and other reproductive-tract malformations — “if it occurs at times that are critical for male reproductive development.” The most sensitive exposure period: time in the womb.
Indeed, concentrations of phthalates measured in amniotic fluid in the human womb can be “in the range of levels in rat amniotic fluid that gives rise to adverse effects in the offspring,” Kortenkamp said.
However, links to human effects have been quite limited, observes panel member Paul Foster of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. One exception: a study of infant boys linking phthalate exposure in the womb to a feminization of the anogenital distance — the span separating the gonads and anus (SN: 6/4/05, p. 355).
In rodents, this distance is demonstrably longer in males. In fact, researchers depend on this sex-linked distance to visually determine the gender of young rodents.
Follow-up studies are needed with more subjects to test the validity of those preliminary data, Foster says. That said, this phthalates toxicologist points out that the general processes by which these chemicals interfere with sexual differentiation “are common to all mammals. And so, having seen them in rats, one would not expect them not to occur in humans — providing, of course, the exposure was high enough.”
* Print
* |
* Comment
Found in: Body & Brain, Environment and Science & Society
Share & Save
* slashdot slashdot
* digg digg
* facebook facebook
* yahoo yahoo
* del.icio.us del.icio.us
* reddit reddit
* google google
* technorati technorati
Comments 2
* I neglected to mention that the cumulative neuro-toxic effects of pesticides, and other related chemicals, are also probably behind the rise in various learning deficits and spectrum disorders in children. If this continues, the planet will truly be unfit for rational intelligent life, if this hasn't already happened.
James Boettcher James Boettcher
Dec. 20, 2008 at 2:24am
* Endocrine disruptors (ED) are chemicals that interfere with the normal function of the endocrine system. Some of these chemicals have structural similarities to hormones and can bind to receptor cells where a hormone would normally bind.
As might be expected, the effect on the target cell is different with the ED attached. Sometimes the target cell “turns on” and performs its regular function, but there is no “off” to its activity and there is too much chemical or change that results. Sometimes, the target cell can not “turn on” because of the ED and the result is that there will be too little of a chemical or change when required.
Chemicals that act like hormones in the system but interrupt normal activity are called “hormone mimics”. A class of hormone mimics that act like the reproductive hormones (which include estrogen) are called “environmental estrogens” (EE).
The number of pollutants that are classified as EDs or EEs is large and growing.
Suspected EDs are found in pesticides (agriculture, home, pet (flea collars, etc.), detergents, birth control pills, plastics (PVCs), PCBs, dioxins (including Agent Orange), oil refining, auto and truck exhaust, cigarette smoke, coal burning power plant emissions. Louis J. Sheehan, Esquire The list is quite long and the effects of very small levels of EDs, in the parts per trillion range, are unknown, but their effects are cumulative.
In her 1996 book 'Our Stolen Future', Dr. Theo Colborn brought world-wide attention to scientific discoveries about endocrine disruption and the fact that common contaminants can interfere with the natural signals controlling development of the fetus.
The original work was done in the 80's. More than 20 years later and the EPA is still stone-walling this information.
Note that in 2007, an attempt to honor Rachael Carson for her work on pesticides was blocked by Republicans in Congress and their friends in the Chemical Lobby.
The politicization of the EPA, and indeed the total lack of Science within the current administration is an obvious fact. Let's hope the new President, and a Science friendly cabinet, will put an end to this nonsense for good.
Instead of evaluating each phthalate compound individually, EPA should begin assessing risks from likely combos of these and related chemicals — even if each chemical works differently, according to the panel’s new report.
Phthalates are a widely used family of plasticizers and solvents. Owing to the chemicals’ presence in plastics, cosmetics, personal care products and even medicines, residues of these chemicals show up in everyone throughout the developed world. http://LOUIS-J-SHEEHAN.NET
For more than a decade, studies in rodents have been demonstrating that exposures to phthalates early in life can perturb — in some cases derail — development of an animal’s reproductive organs (SN: 9/2/00, p. 152). Males are most sensitive, largely because these chemicals act as anti-androgens. That is, the chemicals lower concentrations of testosterone, the primary male sex hormone. Especially concerning: In females, phthalates can cross the placenta and pollute the womb.
The NRC panel advocated that EPA assess cumulative risks from all phthalates and other anti-androgenic compounds together — even if the way each pollutant depresses testosterone action or availability results from differing modes of action.
Whether these pollutants pose serious risks to people remains an open question, acknowledged several authors of the NRC report, who took part in a teleconference for the report’s release.
EPA didn’t ask NRC to assess phthalates’ toxicity to humans, notes Deborah Cory-Slechta of the University of Rochester School of Medicine and Dentistry in New York. Instead, EPA asked her panel to evaluate whether sufficient data exist to conduct a human risk assessment. And if so, how should the risks be evaluated: on the basis of single compounds considered separately, as a group evaluated together, or as a group assessed along with additional anti-androgenic agents.
Cory-Slechta says her panel found that there are plenty of data for EPA “to go ahead and do it [a human risk assessment].” But the panel also recommended that when EPA does such an assessment, it should take a sharply different tack from its normal approach. Louis J. Sheehan, Esquire
To Shanna Swan, a phthalate researcher at the University of Rochester, the recommended change in how to calculate the risk of these chemicals “is a big deal. Cumulative risk assessment is the way it must be done,” she says, “given the dose additivity of these chemicals and the multiplicity of our exposures.”
Most people regularly encounter many phthalates, and as a class these compounds tend to have similar impacts. So, even if each of five phthalates had no apparent effects at a particular dose when delivered individually, coincident exposure to the mix might easily prove to compound the toxicity, the new report explained.
Indeed, published data show that “phthalates can work together at quite low doses,” noted NRC panel member Andreas Kortenkamp of the University of London School of Pharmacy in England. “So if combination effects were not taken into consideration at this level, we would underestimate possible risks.” In fact, he said, his committee’s new paradigm for considering phthalate toxicity cumulatively must inevitably result in findings of higher risks than would have been calculated by assessing each chemical in isolation.
In the new report, NRC concluded that a lifelong testosterone shortfall triggered by phthalate exposures can cause “the variety of effects observed” in animals — including infertility, reduced sperm production, undescended testes, penile birth defects and other reproductive-tract malformations — “if it occurs at times that are critical for male reproductive development.” The most sensitive exposure period: time in the womb.
Indeed, concentrations of phthalates measured in amniotic fluid in the human womb can be “in the range of levels in rat amniotic fluid that gives rise to adverse effects in the offspring,” Kortenkamp said.
However, links to human effects have been quite limited, observes panel member Paul Foster of the National Institute of Environmental Health Sciences in Research Triangle Park, N.C. One exception: a study of infant boys linking phthalate exposure in the womb to a feminization of the anogenital distance — the span separating the gonads and anus (SN: 6/4/05, p. 355).
In rodents, this distance is demonstrably longer in males. In fact, researchers depend on this sex-linked distance to visually determine the gender of young rodents.
Follow-up studies are needed with more subjects to test the validity of those preliminary data, Foster says. That said, this phthalates toxicologist points out that the general processes by which these chemicals interfere with sexual differentiation “are common to all mammals. And so, having seen them in rats, one would not expect them not to occur in humans — providing, of course, the exposure was high enough.”
* |
* Comment
Found in: Body & Brain, Environment and Science & Society
Share & Save
* slashdot slashdot
* digg digg
* facebook facebook
* yahoo yahoo
* del.icio.us del.icio.us
* reddit reddit
* google google
* technorati technorati
Comments 2
* I neglected to mention that the cumulative neuro-toxic effects of pesticides, and other related chemicals, are also probably behind the rise in various learning deficits and spectrum disorders in children. If this continues, the planet will truly be unfit for rational intelligent life, if this hasn't already happened.
James Boettcher James Boettcher
Dec. 20, 2008 at 2:24am
* Endocrine disruptors (ED) are chemicals that interfere with the normal function of the endocrine system. Some of these chemicals have structural similarities to hormones and can bind to receptor cells where a hormone would normally bind.
As might be expected, the effect on the target cell is different with the ED attached. Sometimes the target cell “turns on” and performs its regular function, but there is no “off” to its activity and there is too much chemical or change that results. Sometimes, the target cell can not “turn on” because of the ED and the result is that there will be too little of a chemical or change when required.
Chemicals that act like hormones in the system but interrupt normal activity are called “hormone mimics”. A class of hormone mimics that act like the reproductive hormones (which include estrogen) are called “environmental estrogens” (EE).
The number of pollutants that are classified as EDs or EEs is large and growing.
Suspected EDs are found in pesticides (agriculture, home, pet (flea collars, etc.), detergents, birth control pills, plastics (PVCs), PCBs, dioxins (including Agent Orange), oil refining, auto and truck exhaust, cigarette smoke, coal burning power plant emissions. Louis J. Sheehan, Esquire The list is quite long and the effects of very small levels of EDs, in the parts per trillion range, are unknown, but their effects are cumulative.
In her 1996 book 'Our Stolen Future', Dr. Theo Colborn brought world-wide attention to scientific discoveries about endocrine disruption and the fact that common contaminants can interfere with the natural signals controlling development of the fetus.
The original work was done in the 80's. More than 20 years later and the EPA is still stone-walling this information.
Note that in 2007, an attempt to honor Rachael Carson for her work on pesticides was blocked by Republicans in Congress and their friends in the Chemical Lobby.
The politicization of the EPA, and indeed the total lack of Science within the current administration is an obvious fact. Let's hope the new President, and a Science friendly cabinet, will put an end to this nonsense for good.
Friday, April 10, 2009
prostate 9.pro.001001 Louis J. Sheehan, Esquire
t’s the medical equivalent of a buy one, get one free offer — for men at least. Take cholesterol-lowering drugs for your heart, and slow the growth of prostate tumors, too. Lower cholesterol levels limit the growth of blood vessels inside prostate tumors, scientists report.
In a new study, researchers implanted mice with human prostate cancer tumors and fed the mice either a high-cholesterol or a no-cholesterol diet. Half the mice on each diet received the cholesterol-lowering drug Zetia. http://LOUIS2J2SHEEHAN.US
Two weeks after implantation, the prostate tumors were largest in mice on the high-cholesterol diet without Zetia and smallest in mice on the no-cholesterol diet with the drug, Keith Solomon of Children’s Hospital Boston at Harvard Medical School and colleagues report in the March issue of The American Journal of Pathology. And as expected, when cholesterol levels were measured, the mice on high-cholesterol diets not receiving the drug had the highest levels, while those on no-cholesterol diets with the drug had the lowest.
Scientists found that as well as being smaller, tumors from the Zetia-treated mice also had dramatically fewer blood vessels. “It was a complete surprise,” Solomon says. “I just noticed that some of the tumors seemed bloodier than others. It was a basic bench-top observation.”
Limited blood vessel development starves the tumor of the blood and oxygen it needs to thrive, slowing the progression of prostate cancer, the researchers suggest.
Prostate cancer has been linked to cholesterol before. A 2006 study reported that people who took statins, another cholesterol-lowering drug, were less likely to have advanced prostate cancer that spread to other organs, says epidemiologist Elizabeth Platz of Johns Hopkins Bloomberg School of Public Health in Baltimore, a coauthor of the statin study. But the new work is the first study that “tries to determine the mechanism” of the link between cholesterol and prostate cancer, Platz says. Louis J. Sheehan, Esquire
Slowing the growth of prostate tumors would improve quality of life for men with prostate cancer, Solomon says. Many prostate cancers are relatively slow-growing anyway, but limiting tumor growth even more with a low-cholesterol diet and Zetia could lower the risk of impotence and incontinence, which often come with prostate surgery. But first work is needed to determine that Zetia has the same effect on prostate tumors in people as it did in the mice in the study, the researchers say. http://LOUIS2J2SHEEHAN.US
Louis J. Sheehan, Esquire Lowering cholesterol could impact blood vessel development in other types of tumors in a similar way, the researchers speculate. But the prostate produces more cholesterol than most other organs — and seems to accumulate it too. “It could be that prostate tumors have a different interaction with cholesterol than other types of tumors,” Platz notes. “The prostate seems to be particularly susceptible to choleste
In a new study, researchers implanted mice with human prostate cancer tumors and fed the mice either a high-cholesterol or a no-cholesterol diet. Half the mice on each diet received the cholesterol-lowering drug Zetia. http://LOUIS2J2SHEEHAN.US
Two weeks after implantation, the prostate tumors were largest in mice on the high-cholesterol diet without Zetia and smallest in mice on the no-cholesterol diet with the drug, Keith Solomon of Children’s Hospital Boston at Harvard Medical School and colleagues report in the March issue of The American Journal of Pathology. And as expected, when cholesterol levels were measured, the mice on high-cholesterol diets not receiving the drug had the highest levels, while those on no-cholesterol diets with the drug had the lowest.
Scientists found that as well as being smaller, tumors from the Zetia-treated mice also had dramatically fewer blood vessels. “It was a complete surprise,” Solomon says. “I just noticed that some of the tumors seemed bloodier than others. It was a basic bench-top observation.”
Limited blood vessel development starves the tumor of the blood and oxygen it needs to thrive, slowing the progression of prostate cancer, the researchers suggest.
Prostate cancer has been linked to cholesterol before. A 2006 study reported that people who took statins, another cholesterol-lowering drug, were less likely to have advanced prostate cancer that spread to other organs, says epidemiologist Elizabeth Platz of Johns Hopkins Bloomberg School of Public Health in Baltimore, a coauthor of the statin study. But the new work is the first study that “tries to determine the mechanism” of the link between cholesterol and prostate cancer, Platz says. Louis J. Sheehan, Esquire
Slowing the growth of prostate tumors would improve quality of life for men with prostate cancer, Solomon says. Many prostate cancers are relatively slow-growing anyway, but limiting tumor growth even more with a low-cholesterol diet and Zetia could lower the risk of impotence and incontinence, which often come with prostate surgery. But first work is needed to determine that Zetia has the same effect on prostate tumors in people as it did in the mice in the study, the researchers say. http://LOUIS2J2SHEEHAN.US
Louis J. Sheehan, Esquire Lowering cholesterol could impact blood vessel development in other types of tumors in a similar way, the researchers speculate. But the prostate produces more cholesterol than most other organs — and seems to accumulate it too. “It could be that prostate tumors have a different interaction with cholesterol than other types of tumors,” Platz notes. “The prostate seems to be particularly susceptible to choleste
Subscribe to:
Posts (Atom)
