GLYCOPROTEIN HORMONE ALPHA-SUBUNIT PRODUCTION AND PLURIHORMONALITY IN HUMAN CORTICOTROPH TUMORS - AN IN-VITRO AND IMMUNOHISTOCHEMICAL STUDY

Glycoprotein hormone alpha-subunit (alpha SU) is a recognized product of clinically non-functioning, glycoprotein hormone-secreting and somatotroph adenomas but has not been studied systematically in corticotroph tumours. We have performed immunohistochemistry for alpha SU in a consecutive series of four corticotroph tumours causing Nelson's syndrome, three corticotroph macroadenomas, 12 corticotroph microadenomas and one adrenocorticotrophin-secreting bronchial carcinoid tumour. In addition we have assessed alpha SU secretion in vitro in corticotroph adenomas from two subjects with Cushing's disease and two subjects with Nelson's syndrome. Immunohistochemistry, performed after microwave treatment of sections to enhance antigen retrieval, demonstrated alpha SU positivity in 3/4 Nelson's tumours, 2/3 corticotroph macroadenomas, 7/12 microadenomas and one bronchial carcinoid. Eight of the 13 tumours positive for alpha SU were also immunostained after microwave pretreatment of sections for thyrotrophin (six positive), follicle-stimulating hormone (four positive), luteinizing hormone (three positive), beta-chorionic gonadotrophin (five positive), growth hormone (three positive) and prolactin (two positive) immunoreactivity. In vitro cell cultures of all four tumours studied secreted adrenocorticotrophin and three secreted alpha SU, with the variable presence of luteinizing hormone, follicle-stimulating hormone, thyrotrophin, growth hormone and prolactin, in basal culture. The alpha SU secretion was augmented by phorbol ester (160 +/- 15%, SEM, n = 3 wells; p < 0.01) and 8-bromo-cAMP (138 +/- 8%; p < 0.05) in one tumour. These data indicate that plurihormonality and, in particular, alpha SU elaboration and secretion by corticotroph tumours is more common than hitherto recognized. Possible mechanisms include abnormal or deregulated gene expression, autocrine or paracrine effects or a stem cell origin of tumour. The possible relationship of alpha SU production to corticotroph tumour behaviour and prognosis remains to be established.