Pituitary stem cells could one day be used to treat pituitary hormone deficiencies, according to new research from the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute).
"Pituitary hormone deficiencies, also called hypopituitarism, are associated with significant rates of illness and death. Growth hormone deficiency is the most common type," explained Robin Lovell-Badge of NIMR. "Hypopituitarism can be congenital. For instance, as many as one in 3,500 babies are born with growth hormone deficiency. Alternatively, hypopituitarism can be acquired, particularly after brain injuries. Various studies cite rates of 15 to 90 per cent of traumatic brain injury patients being affected."
The current therapies rely on hormone replacement, but these do not mimic the natural pattern of hormone secretion and are associated with side effects.
Karine Rizzoti, in Dr Lovell-Badge's laboratory at NIMR made use of genetic tools in several lines of mice, one of which was generated by Haruhiko Akiyama of Kyoto University in Japan, to characterise for the first time pituitary stem cells, both in embryos and adults. By following the fate of stem cells in the mouse pituitary gland, she showed that these cells were able to become endocrine cells - the cells which are responsible for secreting hormones into the bloodstream.
In normal conditions, in adult mice, the pituitary stem cells give rise to endocrine cells, although this doesn't happen often compared with embryonic and newborn mice. Instead, they tend to self renew and maintain their identity as pituitary stem cells.
However, the regenerative potential of these stem cells can be enhanced by physiological demand. Estrogen treatment in male mice, and removal of pituitary target organs (such as adrenal glands or testes) were known to stimulate proliferation and generation of new pituitary endocrine cells, but these were thought to come from the division of pre-existing endocrine cells.
This study shows that these two treatments actually induce the pituitary stem cells to proliferate and for some of them to become endocrine cells, enabling them to make a substantial contribution to the pool of newly generated endocrine cells.
"Pituitary hormone deficiencies are associated with significant illness and regeneration of missing endocrine cells would represent a significant improvement over existing treatments," said Dr Rizzoti. "Our study is a first step toward the potential use or control of adult pituitary stem cells to generate new endocrine cells."
They added that the study also provides an ideal model to explore how physiological changes alter stem cell behaviour.
The paper, Mobilized adult pituitary stem cells contribute to endocrine regeneration in response to physiological demand, is published in Cell Stem Cell.
