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

Abstract

ABSTRACT A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and "non-functioning" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with "non-functioning" pituitary tumours 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), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data. In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea 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 tumour samples (Cushing's disease and 1 "non-functioning" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 "non-functioning" pituitary tumours). After 6 months 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. First, in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 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.