Study of Gene’s Hormone Effects Leads to Surprise Insight into Pituitary Tumors

Rathke's cleft cysts are benign, fluid filled growths that develop in the pituitary gland, a small oval-shaped gland near the underside of the brain. Usually, these cysts don't cause symptoms.  However, if they become large enough to compress the organ and surrounding tissues, then they can cause problems with vision and the secretion of hormones from the pituitary gland.  Treatment for these cysts may involve draining the fluid and surgical removal.

Little is known about why these cysts form. The authors of a new paper in the Journal of Clinical Investigation, led by Sally Camper, Ph.D., the Margery Shaw Distinguished University Professor of Human Genetics, have developed a model of Rathke's cleft cysts by breeding mice that lack the gene for a protein called Islet 1 in the developing pituitary gland. 

They discovered that the cysts arise from pituitary stem cells that have adopted the wrong cell fate without the guidance of Islet 1, which normally drives pituitary hormone production. The animal model allowed them to examine the development of the cysts over time and identify markers that could be used by pathologists to diagnose Rathke's cleft cysts. Typically, the cysts are identified using brain scans.

The development of the cysts was a surprise, says Camper. "We were interested in whether the Islet 1 gene has a role in pituitary hormone production the same way it does in the pancreas, where it drives expression of insulin and other pancreatic endocrine hormones." The accidental finding shows how researching the basics of how organs develop can lead to discoveries that are clinically relevant, she adds.

First authors on the paper were Michelle Brinkmeier and Hironori Bando, Ph.D. of the U-M Medical School's Department of Human Genetics.

Paper cited: "Rathke's cleft-like cysts arise from Isl1 deletion in murine pituitary progenitors," Journal of Clinical Investigation. DOI: 10.1172/JCI136745.