Researchers at the University of Gothenburg can now demonstrate previously unexplained processes behind growth therapy. It involves hormonal mechanisms at the cellular level, with focus on a sensitive balance between stem cells and growth hormone.
When children grow in length, it occurs from growth plates, a cartilage structure at both ends of the long bones found in the arms and legs. The growth plates contain special stem cells that continuously produce new cartilage cells, which are converted into bone tissue.
In the case of growth disorders in children, with a height significantly below the average for their age and sex, injections of growth hormone are the most common treatment. In the development of growth hormone therapy, the University of Gothenburg has played a historically important role
Previous research has shown that growth hormone acts directly on the growth plate. However, it has been unclear which cells are targeted by growth hormone and how.
A delicate balance between two roles
In the current study, published in the journal PNAS, researchers have discovered through advanced experimental mouse models that growth hormone directly controls the behavior of stem cells in the growth plate.
When stem cells cannot sense growth hormone, their ability to generate new cartilage cells is greatly reduced, which leads to impaired growth. And conversely, when growth hormone levels are too high, stem cells are driven to produce more cartilage cells. However, excess growth hormone simultaneously reduces the number of stem cells.
This reveals the dual role of growth hormone and a delicate balance: Growth hormone stimulates growth, but excessive exposure can deplete the very cartilage stem cells that are needed for long-term bone development.
Insights that can refine treatment
The findings also provide a potential explanation for certain observations made in the care of children with growth disorders, particularly where treatment with growth hormone has not produced the expected long-term effects.
The research was led by Andrei Chagin, professor of molecular medicine at the Sahlgrenska Academy at the University of Gothenburg:
“These findings provide important new insights into the mechanisms of growth hormone action and may ultimately contribute to refining growth hormone treatments and making them more effective for children with growth disorders,” he says.