Most of what we learn about cholesterol concerns its involvement in heart disease and clogging up arteries. However, the waxy, fat-like substance also plays a vital role in growth of cells and is an essential building block in their production of steroids and hormones.
Image credit: D. Ory
Now, a new study from Washington University School of Medicine in St. Louis, MO, reveals how a key molecule that controls the trafficking of cholesterol inside cells affects their ability to make steroid hormones that support pregnancy and trigger puberty.
Writing in the journal Cell Metabolism, the researchers say their findings offer important clues about the causes of infertility and drivers of early puberty, especially in girls.
They suggest too much of the key molecule likely impairs proper steroid hormone production, resulting in infertility, while too little could lead to premature sexual maturation.
The key molecule they identified is a small strand of RNA from a class known as small nucleolar RNA, or snoRNA. Its name is U17 snoRNA.
Daniel S. Ory, senior author and professor of medicine, says he and his colleagues were surprised by their findings because, typically, snoRNAs are involved in the production of proteins and are not well known for doing other things such as influencing the production of steroids.
“This is one of several hundred snoRNAs,” he notes, “Clearly, some of them have functions beyond the traditional understanding of snoRNAs, and perhaps they should be studied more systematically.”
Previously, the team had found high levels of U17 snoRNA in the ovaries and testes of mice. These organs make steroid hormones like progesterone and testosterone.
In the new study, they showed that at birth, mice have high levels of U17 snoRNA, which gradually decline as the animals grow and mature.
When the mice reach sexual maturity – at 8 weeks – U17 snoRNA levels are very low and this increases production of steroid hormones.
Prof. Ory explains what this might mean:
“The ovaries need to make steroids to support pregnancy when the mice reach sexual maturation. So we think this small RNA is at least one of the regulators of the processes that govern when a mouse becomes fertile.”
For the next phase of the study, the team took a look inside hamster ovary cells, paying particular attention to cholesterol and mitochondria.
Mitochondria are the tiny factories that produce units of chemical energy for fueling cell activity. But they also have another role – they make steroids, using cholesterol as the main ingredient.
Prof. Ory and colleagues found that in cells lacking U17 snoRNA, the cholesterol was ushered into the cell’s mitochondria. But in cells that had an abundance of U17 snoRNA, the cholesterol did not reach the mitochondria, and without their raw material, the cells did not make any steroids.
The team found when they tweaked U17 snoRNA levels in normal, immature mice, it allowed cholesterol to travel to the mitochondria, triggering steroid production in the mouse ovaries.
Prof. Ory says they have yet to test whether these early-puberty mice are able to breed, “but we certainly increased levels of pregnenolone and progesterone, which are steroids necessary to support pregnancy.”
He says he and his colleagues plan to investigate U17 snoRNA further and look at how it works with proteins to increase or decrease cholesterol trafficking into mitochondria and subsequent steroid production.
The findings should also prompt further investigation into how hormone-like chemicals in our environment might affect puberty and fertility, notes Prof. Ory:
“There are environmental cues that might be involved. We need to work with our colleagues in fertility research as we think about future directions for this work.”
Meanwhile, Medical News Today recently learned about another new cell discovery that may explain some ovarian disorders. In the journal Nature Communications, National Institutes of Health researchers reveal that theca cells – essential for making hormones that support ovarian follicle growth – come from two sources, one inside and the other outside the ovary.