Scientists have discovered a hormone that may solve a long-standing biological mystery.
“Proving you’ve identified a new hormone is difficult — it’s a chemical signal that directs the behavior of cells far away, often through the bloodstream. To prove it for sure, you need to see where it’s made, what tissues it affects, and whether it can be present in the bloodstream,” said the senior study author. Holly Ingraham“This is a very interesting study,” the professor and associate dean of cellular and molecular pharmacology at the University of California, San Francisco, told Live Science.
“Most have been discovered, so to actually discover a new hormone is pretty novel.” Dr. Sandeep Khosla“They make a pretty compelling case that this is indeed a hormone,” said Dr. Gregory B. Schneider, a physician-scientist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study.
Khosla said scientists had previously found the substance in mammals, including humans, but hormoneThe new study, published in the journal Neuroscience on Wednesday (July 10), found that the chemical, which the researchers dubbed the “maternal brain hormone,” travels from the brain to bone-forming cells, where it helps form bone. Nature.
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This bone formation is pregnancy“When milk production begins, estrogen levels drop sharply and the demand for calcium soars. Normally, estrogen strengthens bones and protects them from calcium robbery, so it was unclear how bones retain so much strength during lactation and then regain it so quickly after weaning.”
The new hormone “adds a previously unknown and important piece to the overall biology,” Khosla told Live Science. What’s more, the researchers showed that the new hormone, which is important in the postpartum period, can also promote bone growth in men.
“This is an equal opportunity hormone that acts on bone and skeletal stem cells in both men and women,” Ingraham says. “If we could develop this into a therapeutic treatment, [it] “It works for both men and women.” The hormone could theoretically speed up fracture repair, treat osteoporosis and prevent early bone loss. Treatment-induced bone loss.
Searching for hormones
The new research is based on studies in mice. Published in 2019Ingraham and colleagues have discovered a way to increase bone density and strength by up to 800 percent. This dramatic effect is seen in the brain. Hypothalamusa structure that makes hormones. Blocking estrogen in certain cells in the hypothalamus promoted bone growth, but this only worked in female mice, not males, suggesting that this particular pathway is only present in females.
The researchers theorized that when estrogen is turned off, these cells in a woman’s brain somehow tell the body to direct energy towards bone growth. The question was, how do these cells get that message across? So in the new study, the researchers looked for molecules in the blood that might deliver that message.
Ingraham told Live Science that the quest is like looking for a needle in a haystack because the hormone is present in the blood in “tiny, tiny amounts.”
The team first identified blood as the culprit by blocking estrogen signaling in mice that developed extremely thick bones. Normal mice injected with the blood of these modified mice showed dramatic bone growth. The team also found that the bone-growing enzyme, β-lactamase, stimulated bone growth. Stem Cells They then transplanted whole bones into various parts of the modified mice, and these also promoted growth, suggesting that the hormone is potent and circulates widely.
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The team then looked at gene activity in the hypothalamus and found that certain genes in these cells were much more active in the big-boned mice. CCN3which codes for instructions for proteins (proteins that the researchers suggest should be called “maternal brain hormones”).
Not much is known about the CCN3 protein, but historically, people didn’t think of it as a hormone — it was thought to act locally rather than enter the circulation, Ingraham said. Still, the group’s experiments suggested that this protein was the hormone they were looking for.
This is particularly novel because hormones made in the hypothalamus normally Pituitary gland The pituitary gland sends messages to the body through the hypothalamus, but in this case, hormones made by the hypothalamus “go straight to the bone,” Khosla said.
The team also demonstrated that bone-strengthening hormones could speed up fracture healing in older mice.
“When we looked at the fracture repair data, we knew this was absolutely real,” Ingraham said. “To see this kind of repair in a two-year-old male mouse is really quite remarkable.”
Finally, scientists have found that CCN3 naturally increases in the brains of female mice after birth. Blocking this increase causes the mice to rapidly weaken their bones as they continue to lactate. This increase in CCN3 has not yet been confirmed in humans, Khosla said, but the mouse data suggests that the hormone is key to keeping bones strong during lactation. But at this point, it’s unclear how that switch is actually flipped in the brain.
“What on earth is this? [postpartum] “What physiological event causes neurons in the brain to activate this hormone?” Ingraham said. “We don’t know yet.” Solving that mystery will require much more research, and in the process, he said, new hormones may be uncovered.
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