Study of cholesterol in cells offers clues on infertility and early puberty

18 Jun

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.

Cholesterol – here in hamster ovary cells – is a building block of

steroid hormones that trigger puberty and support pregnancy.
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


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


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


“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


U17 snoRNA levels decline from birth to maturity

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


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


Could hormone-like environmental chemicals affect puberty and fertility?

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


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.

Written by Catharine Paddock PhD