Research led by Dr. Jacques Drouin’s team at the Montreal Clinical research Institute (IRCM), published in Stem Cell Reports, highlights the key role of certain immature pituitary cells in the proper functioning of stress-related hormones. This discovery links, for the first time, hormonal balance to the very organization of cells within the pituitary gland and describes a new cell type that could also be involved in tumor formation.
At the heart of the matter
The adrenal glands produce essential hormones called glucocorticoids, which help the body respond to stress and regulate metabolism. Their production is controlled by a pituitary hormone, ACTH. In turn, glucocorticoids inhibit ACTH production—this is known as a negative feedback mechanism. This self-regulating system is fundamental to maintaining the body’s balance. When it becomes disrupted, it can contribute to major health problems, such as metabolic syndrome.
Using cutting-edge technology to analyze gene activity cell by cell (single-cell RNA sequencing), the researchers identified a new cellular state, which they named “pre-corticotrophs.” These are cells in transition between pituitary stem cells and the specialized cells that produce ACTH.
The researchers observed that, in the absence of the inhibitory effect of glucocorticoids, these precursor cells proliferate more under the influence of a key factor called Tpit. They also uncovered a local cell-to-cell communication mechanism, sensitive to glucocorticoids, involving a molecule known as BDNF (brain-derived neurotrophic factor). This signal plays an important role in establishing, after birth, the size and organization of the pituitary gland.
Important implications
By revealing the existence of these precursor cells and the signal that guides their transformation into mature cells, this major study provides new insights into how the pituitary maintains balance with the adrenal glands. It also paves the way for a better understanding of certain hormonal disorders and pituitary tumors.
This work was funded by the Canadian Institutes of Health Research (CIHR).
