CYTOKERATIN DISTRIBUTION AND FUNCTIONAL-PROPERTIES OF GROWTH-HORMONE PRODUCING PITUITARY-ADENOMAS

In addition to its structural function, cytokeratin may have other imp ortant roles within cells. We have reported that in growth hormone-pro ducing adenomas (GH cell adenomas), two distinct types can be recogniz ed by their cytokeratin distribution patterns (dot-like or perinuclear pattern) and that each type has different clinicopathological and end ocrinological properties. To confirm these phenomena in a larger serie s and to clarify the significance of different cytokeratin distributio n patterns, we studied cytokeratin localization in 70 GH cell adenomas from acromegalic patients. Type 1 adenomas (15) almost exclusively (> 98%) composed of cells with a prominent, dot-like distribution; type 2 adenomas (36) comprised of cells with perinuclear cytokeratin; and ty pe 3 adenomas (11) comprised of both cell types were separated. The re maining 8 did not exhibit a distinct distribution pattern. By electron microscopic immunocytochemistry for cytokeratin, dot-like distributio n corresponded to fibrous bodies, whereas perinuclear distribution rep resented immune deposition in the perinuclear zone. Immunohistochemist ry for GH, prolactin, beta-thyrotropin, and alpha-subunit of glycoprot ein hormones revealed a reduced expression of these hormones in type 1 adenomas, compared with types 2 and 3 adenomas. In normal pituitary g lands, almost all GH cells showed a perinuclear cytokeratin distributi on, and only a few GH cells exhibited a dot-like pattern. These findin gs suggest that a dot-like cytokeratin distribution in GH cells may be pathological (a change from physiological perinuclear distribution) a nd that adenomas with such a distribution may reduce endocrine activit ies as a result of unknown factors.