Other The gut microbiome can influence hormone levels (Sep 2024, mice) Hypopituitarism in Sox3 null mutants correlates with altered NG2-glia in the median eminence and is influenced by aspirin and gut microbiota

[Michael Harrop]

https://medicalxpress.com/news/2024-09-gut-microbiome-hormone-mouse.html
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1011395

People with mutations in a gene called Sox3 develop hypopituitarism, where the pituitary gland doesn't make enough hormones. It can result in growth problems, infertility and poor responses of the body to stress.

He also examined the number of NG2 glia in the Crick mice, finding that these were also at normal levels, suggesting that the Crick-fed microbiome was somehow protective against hypopituitarism.

To confirm this theory, Christophe transplanted fecal matter retained from NIMR mice into Crick mice, observing that the Crick mice once again showed symptoms of hypopituitarism and had lower numbers of NG2 glia.

Although the exact mechanism is unknown, the scientists conclude that the make-up of the gut microbiome is an example of an important environmental factor having a significant influence on the consequences of a genetic mutation, in this case influencing the function of the hypothalamus and pituitary gland.

Click to shrink...

Abstract​

The median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factor SOX3/Sox3 result in hypopituitarism, and this is likely of hypothalamic origin.

We demonstrate here that the absence of Sox3 predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism in Sox3 mutants.

Our study highlights a central role of NG2-glia for ME function during a transitional period of post-natal development and indicates their sensitivity to extrinsic signals.

Click to shrink...

Author summary​

The hypothalamus, a complex structure in the ventral-medial brain, has many critical functions, including controlling the secretion of hormones from the pituitary gland. In turn, these hormones regulate many important physiological functions, such as growth, stress responses and reproduction, and insufficient levels result in significant morbidity and even mortality if untreated. The hypothalamus is linked to the pituitary via the median eminence (ME), where information is exchanged.

Previously, we, and others, have highlighted the importance of SOX3/Sox3 for the hypothalamo-pituitary axis, because mutations in this gene result in a reduction of all pituitary hormones, or hypopituitarism, in both humans and mice.

Here we demonstrate that loss of Sox3 in mice affects specialised supporting cells of the ME called NG2-glia and that this only occurs only after weaning. The defects correlate with abnormal development of the hormone-secreting cells of the pituitary and the onset of hypopituitarism. We also show that external factors such as aspirin or changes in gut microbiota can rescue both the hypopituitarism in Sox3 mutants and renewal of the ME NG2-glia.

In conclusion, our data suggest a critical role for NG2 glia in the ME for the maturation of hormone producing cells in the pituitary and that these NG2 glia are sensitive to the loss of Sox3 and to extrinsic factors. This argues that aspirin, altering gut microbiota, or perhaps just dietary modulation may be of benefit in treating certain cases of hypopituitarism.

Click to shrink...