Hormone Secretion by Dispersed Cell Cultures of Human Pituitary Adenomas: Effects of Theophylline, Thyrotropin-Releasing Hormone, Somatostatin, and 2-Bromo-α-Ergocryptine*

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Abstract
Basal and modulated secretion of PRL and GH by dispersed cell cultures of human somatotropic, lactotropic, and mixed somatotropic-lactotropic adenomas has been examined. Twenty-four-hour secretion of PRL by a normal pituitary, a lactotropic, and a mixed adenoma increased with time in culture. The secretion rate from a mixed adenoma had increased 18-fold by day 20 over that observed on day 1, 225 µg PRL being produced from 4 X 105 cells. PRL secretion was still elevated after 36 days of culture. GH secretion always decreased rapidly from day 1. Initial GH secretion in cultures of a somatotropic adenoma was 18-fold of that from the same number of normal pituitary cells. Theophylline (10-2 M) significantly stimulated GH secretion by somatotropic and mixed adenoma cells during a 4-h incubation after 4 and 28, but not 49, days in culture. PRL secretion was only stimulated at 28 days. TRH stimulated PRL and GH secretion from adenomas in a dose-dependent manner, with 10 ng/ml TRH being maximal. Somatostatin alone at doses up to 100 ng/ml had no consistent effect on GH secretion but completely blocked the 2-fold stimulation induced by 10-2 M theophylline. Bromocriptine (2-bromo-α-ergocryptine) inhibited basal PRL and GH secretion with increasing effects up to the maximum used (10 µg/ml) and virtually abolished the theophylline-induced stimulation of GH and PRL secretion at this dose. It is concluded that dispersed cell cultures of human pituitary adenomas can be satisfactorily maintained for at least 28 days, and, during this period, demonstrate autonomous secretion of PRL but not GH. The modulation of PRL and GH secretion by various agents indicates the value of this technique for the direct study of functioning human pituitary adenomas. (J Clin Endocrinol Metab49: 120, 1979)

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