PRODUCTION OF ALPHA-SUBUNIT OF GLYCOPROTEIN HORMONES BY PITUITARY SOMATOTROPH ADENOMAS IN-VITRO

Somatotroph adenomas of the pituitary secrete growth hormone in excess and are associated with acromegaly. Morphologically, they can be sepa rated into two entities, densely and sparsely granulated variants. It has been shown that a number of somatotroph adenomas produce alpha-sub unit of glycoprotein hormones; however, it is not clear whether alpha- subunit production correlates with tumor cell morphology. We studied 3 2 surgically removed pituitary somatotroph adenomas in tissue culture to determine structure-function correlations of growth hormone and alp ha-subunit production. All tumors were classified on the basis of deta iled histological, immunocytochemical and electron-microscopic studies . Fifteen tumors were densely granulated and 17 were sparsely granulat ed. In addition to growth hormone, all 15 densely granulated tumors re leased a-subunit in vitro, whereas of the 17 sparsely granulated tumor s only 4 released alpha-subunit: moreover, the mean baseline levels of alpha-subunit were significantly higher in densely granulated adenoma s than in sparsely granulated adenomas. Parallel response of release o f both hormones was found during stimulation with growth hormone-relea sing hormone or thyrotropin-releasing hormone and during suppression w ith somatostatin or bromocriptine in densely granulated tumors. alpha- subunit response to stimulation or suppression could not be determined with significance in sparsely granulated tumors because of low basal levels. The results indicate that alpha-subunit production and release is characteristic of densely granulated somatotroph adenomas and that alpha-subunit is coregulated with growth hormone by adenohypophysiotr opic substances; in contrast, alpha-subunit production by sparsely gra nulated somatotroph adenomas is rare and, when present, much lower in quantity. Our studies confirm that densely and sparsely granulated som atotroph adenomas represent separate entities.