Organ culture of human somatotrophic pituitary adenomas: ultrastructure and growth hormone production.

Abstract

Ten somatotrophic adenomas removed from acromegalic patients and fragments of the non-tumoural surrounding pituitary were submitted to organ culture for periods of up to one month. Electron microscopic observation shows that these tumours retain their histological differentiation throughout the culture period. The cell morphology of the cultured tumours remains essentially unchanged and in particular the secretory granules keep their initial size (150 and 130 nm). However, the granules disappear gradually so that most of the cells look chromophobic by the 4th week of culture, and numerous lysosomes as well as autophagic figures appear at the same time. The hGH concentration in the culture medium has been measured of 4 adenomas. It is very high (10-fold greater than that from non-tumoural pituitary medium) during the first week (range 200-300 mug/ml). It still remains very high in the same experiments until the second week of culture in one experiment (200 mug/ml). After incubation of cultures with 3-H-leucine 3 H-hGH is obtained in the medium giving evidence of hormone synthesis by adenoma cells in culture. 3-H-hGH represents 40 percent of 3-H-proteins in the culture medium and gives the same elution pattern as standard hGH on Sephadex G 100 chromatography. A certain degree of correlation is observed between morphological and biological results: the greatest hGH production is obtained from explants which maintain the best histological appearance.