TISSUE CULTURE STUDIES ON HUMAN PITUITARY TUMOURS: LONG TERM RELEASE OF ANTERIOR PITUITARY HORMONES INTO THE CULTURE MEDIUM

Abstract

The length of time that human pituitary tumors are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions was determined and the spectrum of hormone release by functioning and non-functioning pituitary neoplasms was studied. Fragments from the pituitary tumors of 10 patients (1 Cushing''s disease, 2 with amenorrhea-galactorrhea, 3 with acromegaly and 4 with non-functioning pituitary tumors) and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by specific radioimmunoassays at the end of each wk in culture. Hormone release was surveyed from 6 wk-6 mo. depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial wk of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumors (1 amenorrhea-galactorrhea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumor samples (Cushing''s disease and 1 non-functioning pituitary tumor). The media of the remaining 4 tumors contained at least 3 of the 6 hormones (1 amenorrhea-galactorrhea and 3 non-functioning pituitary tumors). After 6 mo. in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. In the media from 5 of the 12 cultures from both controls and tumors, Prl concentrations increased after 50-80 days culture. This increase usually lasted for several wk before Prl levels again began to decline. The 2nd unusual finding occurred in a tumor from a patient with acromegaly in the media of which hGH levels rose from 60-800 ng/ml between days 125 and 174. These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.