Critical Reviews in Oncology/Hematology 28 (1998) 73–90 The role of cytokines in the normal and neoplastic pituitary S. Tsagarakis a, *, G. Kontogeorgos b,c , K. Kovacs c a Department of Endocrinology, Eangelismos Hospital, Hypsilantou Street, 106 76 Athens, Greece b Department of Pathology, G. Gennimatas General Hospital of Athens, Athens, Greece c Diision of Pathology, Department of Laboratory Medicine, St. Michael’s Hospital, Uniersity of Toronto, Toronto, Ontario, Canada Accepted 28 January 1998 Contents 1. Introduction .............................................. 74 1.1. Normal pituitary function — an overview .......................... 74 1.2. General aspects of pituitary – immune interactions ..................... 75 2. Expression of cytokines and cytokine receptors by the normal pituitary ............ 75 2.1. Methodology .......................................... 75 2.2. Pituitary-derived cytokines ................................... 76 2.2.1. Interleukin-1 (IL-1) peptide family.......................... 76 2.2.2. Interleukin-2 (IL-2) .................................. 76 2.2.3. Interleukin-6 ...................................... 77 2.2.4. LIF (leukemia inhibiting factor) ........................... 77 2.2.5. MIF (macrophage migration inhibitory factor) .................. 78 2.2.6. Other cytokines .................................... 78 3. The role of cytokines on pituitary function ............................ 78 3.1. Experimental approaches ................................... 78 3.2. Hormone release ........................................ 79 3.2.1. ACTH .......................................... 79 3.2.2. TSH ........................................... 79 3.2.3. GH ........................................... 79 3.2.4. PRL ........................................... 79 3.2.5. Gonadotropins (FSH/LH) .............................. 79 3.3. Pituitary cell proliferation and differentiation ........................ 80 4. Integrated actions of cytokines on pituitary-dependent hormonal functions .......... 80 4.1. Pituitary – adrenal axis ..................................... 80 4.2. Pituitary – thyroid axis ..................................... 81 4.3. Pituitary GH release ...................................... 81 4.4. Pituitary – gonadal axis ..................................... 81 4.5. Summary............................................. 82 5. Cytokines and pituitary tumor formation ............................. 82 5.1. Pathogenesis of pituitary tumors ............................... 82 5.2. Oncogenes ............................................ 82 5.3. Tumor suppressor genes .................................... 83 5.3.1. p53 gene......................................... 83 5.3.2. Retinoblastoma gene ................................. 83 5.3.3. Multiple endocrine neoplasia type 1 (MEN-1) gene ................ 83 5.3.4. Pituitary cytogenetics ................................. 83 * Corresponding author. Tel.: +30 310 7249476; fax: +30 301 7252250. 1040-8428/98/$ - see front matter © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S1040-8428(98)00005-5