Project Summary:
One in 10 people will develop pituitary adenomas (PAs) in their lifetime. While PAs are often benign, they are still considered brain tumors, and when secretory, are associated with serious syndromes and contain the possibility of recurrence after surgical resection. Per the National Cancer Institute, Wisconsin is above the national average and shows a trend for the onset of cancer incidence in the brain and other nervous systems. While surgery is a common treatment for PA, this is an invasive procedure. Therefore, establishing non-surgical treatment options for pre-surgical and recurring tumors will improve the clinical care of Wisconsin residents with PAs.
The pituitary is the pea-sized organ sitting at the base of the brain, often called the “master gland of the endocrine system.” In its limited space, the pituitary is surrounded by important neural and vascular structures essential for proper vision and cerebral circulation. Controlled stimulation of the six hormone-secreting cell types that compose the anterior pituitary releases specific hormones into the bloodstream to induce organ function. For example, stimulation of corticotroph cells from the hypothalamus produces the proopiomelanocortin (POMC) polypeptide, which is processed into adrenocorticotropic hormone (ACTH) and released into the bloodstream for subsequent stimulation of cortisol secretion by the adrenal cortex. Decreasing the expression of POMC will result in lower cortisol levels, such as when the transcription of POMC is inhibited by glucocorticoids interacting with corticotroph cells.
PAs arise from the adenomatous growth of specific pituitary cell types and can alter normal hormone secretory function. In some cases, PAs secrete excess hormones in the face of reduced restraint from negative feedback mechanisms. Hormone hypersecretions can be associated with serious illness. For example, corticotroph adenomas hypersecreting ACTH may result in excessive cortisol production, leading to Cushing Disease. Therefore, the need to control cortisol levels is uniquely important to Wisconsin residents with Cushing disease.
This project aims to meet that need by expanding ongoing basic research into the molecular mechanisms responsible for ACTH hypersecretion in corticotroph adenomas associated with Cushing disease.