A discovery by scientists at UC Riverside may open up new ways to control steroid hormone–mediated processes, including growth and development in insects as well as sexual maturation, immunity, and cancer progression in humans. In a study published yesterday in Developmental Cell, researchers used a well-studied fruit fly model to show that a transporter protein is needed for the hormone ecdysone to pass into cells.
Steroid hormones, which are produced by glands of the endocrine system, must enter cells to exert their biological effects. For decades, the consensus among scientists has been that these chemicals slip freely across cell membranes with no help from cellular transporters. This new study challenges that idea, describing a defined passageway through which steroid hormones are imported into cells.
The insect hormone studied, ecdysone, activates the genes required for metamorphosis and molting as an insect moves from one stage of its life cycle to the next. Since animal development is a precise process, the team hypothesized that the intake of required hormones might be regulated.
"Although the simple diffusion model has been prominent for all steroid hormones to date, it seemed logical from a physiological perspective that cells would regulate ecdysone uptake to achieve better control of its concentration," says senior author Naoki Yamanaka of UCR.
Using two separate genetic screens, the researchers identified a potential gatekeeper—a transporter they named Ecdysone Importer (EcI). They then used the CRISPR-Cas9 gene-editing tool to create fruit flies without this transporter, which completely halted their development.
Yamanaka will now study the same transport pathway in mosquitoes, in hopes of developing chemicals that inhibit steroid hormone entry into cells as a new form of pest control. Another UCR team is also searching for similar transporters in humans.
"If these transporters are found in humans, it will represent a paradigm shift in endocrinology," Yamanaka said. "It would also open up the exciting possibility of developing chemical reagents that manipulate steroid hormone entry into cells, not just in insects but in humans. This could lead to new ways to manipulate a variety of steroid-related processes ranging from immune responses to cancer progression."
Image: UC Riverside researchers have shown that membrane transporters (green) guide steroid hormones (orange circles) into cells, challenging a long-standing paradigm in endocrinology that simple diffusion is responsible for such transport. Image courtesy of Haga-Yamanaka Lab, UC Riverside.