Summary: Researchers have discovered that mutations in the Sox3 gene cause hypopituitarism. Hypopituitarism is a condition in which the pituitary gland produces insufficient hormones, leading to growth problems and infertility. In a study using mice, researchers discovered that mutations in Sox3 affect brain cells called NG2 glia, which are essential for hormone production.
Treating mice with aspirin or altering the gut microbiome restored NG2 glial levels and reversed hypopituitarism. These findings suggest that both aspirin and gut bacteria could be studied as potential treatments for people with Sox3 mutations or other hormone-related diseases.
Important facts:
Sox3 mutations affect NG2 glial cells in the brain and cause hypopituitarism. Aspirin treatment restored NG2 glial levels and reversed hormone deficiency in mice. Changes in the gut microbiome protected mice from symptoms of hypopituitarism.
Source: Francis Crick Institute
People with mutations in a gene called Sox3 develop hypopituitarism, where the pituitary gland doesn’t produce enough hormones. It can cause stunted growth, infertility, and poor body response to stress.
In a study published today in PLOS Genetics, Crick University scientists removed Sox3 from mice and caused them to develop hypopituitarism around the time they were weaned (when they started eating solid food).
They found that mutations in Sox3 significantly affect the brain’s hypothalamus, which instructs the pituitary gland to release hormones. But this gene is normally activated in several types of brain cells, so the first challenge was to find out which specific cells are most affected by its absence.
The researchers observed a decrease in the number of cells called NG2 glia, suggesting that these cells play an important role in inducing the maturation of pituitary cells around weaning. However, this was not known until now. This may explain the associated effects on hormone production.
The team then treated the mice with low doses of aspirin for 21 days. This increased the number of NG2 glia in the hypothalamus and reversed the symptoms of hypopituitarism in mice.
Although it is not yet clear how aspirin produced this effect, the results of this study suggest that aspirin may be considered as a potential treatment for people with Sox3 mutations and other conditions in which NG2 glia are impaired. This suggests that it may be possible.
Accidental discovery reveals role of gut bacteria in hormone production
When the National Institute of Medical Science (NIMR) merged with Click in 2015, mouse embryos were transferred from the former building to the latter, including mice with the Sox3 mutation.
When these mice reached the weaning stage at Click Garden, the researchers were surprised to find that the mice no longer had the expected hormone deficiencies.
After investigating a number of possible causes, lead author Christophe Galiché compared the microbiomes (bacteria, fungi, and viruses that live in the gut) of Crick Institute mice and NIMR mice, and determined their composition and diversity. We observed some differences in gender. This may be due to changes in diet and water environment due to relocation.
He also looked at the number of NG2 glia in click mice and found that these were also at normal levels, suggesting that the microbiome that click mice feed on is somehow protective against hypopituitarism. suggested that.
To confirm this theory, Kristoff transplanted feces collected from NIMR mice into click mice and observed that the click mice once again showed symptoms of hypopituitarism and had a reduced number of NG2 glia. did.
Although the exact mechanism is unknown, scientists believe that the composition of the gut microbiome is an example of an important environmental factor that can profoundly influence the outcome of genetic mutations, and in this case, the function of the hypothalamus and pituitary gland. It is concluded that it affects gland.
Christophe Galiché, former senior research scientist at Click and current research operations manager at Sainsbury’s Wellcome Center, said: “Changes in the gut microbiome reversed hypopituitarism in mice lacking Sox3. It was quite surprising how important it is to be aware of all the variables, including the microbiome, when working with animals in research, and how their upbringing can affect nature. I realized that again.”
Robin Lovell-Budge, group leader in Crick University’s Stem Cell Biology and Developmental Genetics Laboratory, said: “Hypopituitarism can be caused by trauma or rare mutations and has serious implications for overall health. There is a possibility that it will be given.” Our research not only suggests potential treatment options but also highlights how important the gut-brain connection is.
“The next steps in this research will be to elucidate exactly how aspirin and the microbiome affect NG2 glia, and to study this effect in humans so that these relatively accessible interventions can be used in the pituitary gland. to see if it can help treat hypofunction.”
About this microbiome and genetics research news
Author: Claire Green
Source: Francis Crick Institute
Contact: Claire Green – Francis Crick Institute
Image: Image credited to Neuroscience News
Original research: Open access.
“Sox3-null hypopituitarism is dependent on median NG2 glia and influenced by aspirin and gut microbiota” by Christophe Galichet et al. PLOS Genetics
abstract
Sox3-null hypopituitarism depends on median NG2 glial eminence and is influenced by aspirin and gut microbiota
The median eminence (ME), located at the base of the hypothalamus, is an important center of information exchange between the brain and pituitary gland. We and others have previously shown that mutations or duplications affecting the transcription factor SOX3/Sox3 cause hypopituitarism, which is likely to originate from the hypothalamus.
We demonstrate here that despite the embryonic onset of SOX3 expression, lack of Sox3 primarily affects ME with a phenotype that first occurs in young animals. In the pituitary gland, decreased hormone levels are correlated with a lack of endocrine cell maturation.
In parallel, ME NG2-glial regeneration and oligodendrocyte differentiation potential are affected. Furthermore, we show that low-dose aspirin treatment, which is known to affect changes in NG2-glia and gut microbiota, rescues both the proliferative abnormalities and hypopituitarism in Sox3 mutants.
Our study highlights the central role of NG2-glia for ME function during the transition period of postnatal development and shows that they exhibit sensitivity to extrinsic signals.
