Tissue inhibitors of metalloproteinase-expressing cells in human anterior pituitary and pituitary adenoma

Extracellular matrix (ECM) is essential in tissue physiology and pathologic conditions such as tumorigenesis. It affects tumor cell behavior, proliferation, and metastasis. Pituitary adenomas differ in their clinical characteristics, including ECM deposition, and we recently reported that the characteristics of collagen-producing cells differed between control human anterior pituitary gland and pituitary adenomas. ECM deposition is not defined solely by production; degradation and maintenance are also important. Tissue inhibitors of metalloproteinases (TIMPs) help maintain ECM by inhibiting degradation caused by matrix metalloproteases. The present study attempted to characterize TIMP-expressing cells in the human anterior pituitary. Specimens of human pituitary adenomas and control pituitary were obtained during surgery, and in situ hybridization for TIMP1, TIMP2, TIMP3, and TIMP4, followed by immunohistochemistry, was used to characterize TIMP-expressing cells. TIMP expression exhibited a distinct pattern in the human anterior pituitary. Azan staining showed that fibrous matrix deposition varied among pituitary adenomas and that the area of fibrosis was associated with the number and number of types of TIMP3-expressing cells. These results suggest that TIMPs are important in the maintenance of ECM in human pituitary and that TIMP expressions are altered in fibrosis associated with pituitary adenoma.