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Adrenocorticotropin and Lipotropin Secretion by Dispersed Cell Cultures of a Human Corticotropic Adenoma: Effect of Hypothalamic Extract, Arginine Vasopressin, Hydrocortisone, and Serotonin^*

Departments of Medicine and Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital London W12 OHS Pituitary Hormone Laboratory and Department of Chemical Endocrinology, St. Bartholomew’s Hospital London, EC1A, United Kingdom

Address requests for reprints to: Dr. K. Mashiter, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS, United Kingdom.

Basal and modulated secretion of ACTH and lipotropin (LPH) by cultures of trypsin-dispersed cells of a biopsy of a human corticotropic adenoma have been examined. ACTH secretion was detectable throughout the period of culture (13 days) but declined steadily from an initial production rate of 238 ± 124 ng/3 x 10⁵ cells/12 h. The time course of secretion showed a slower phase over the first 4 h, with increases up to 12 h. An extract of rat stalk median eminence caused a significant (P < 0.005) dose-dependent increase in both ACTH and LPH secretion during 30 min. The patterns of response for ACTH and LPH were very similar; both exhibited a decline in the basal release of peptide subsequent to the period of stimulation. The addition of hydrocortisone (0.2 µg/ml) did not suppress basal ACTH secretion during 30 min but significantly (P < 0.05) inhibited stimulation produced by rat stalk median eminence extract. Arginine vasopressin (dose range, 1-9 ng/ml) significantly (P < 0.025) stimulated both ACTH and LPH secretion during 30 min. The patterns of response were again very similar. Serotonin (dose range, 0.01-10 µg/ml) did not affect ACTH secretion during incubations of 30 min to 4 h.

The results obtained with the cell cultures of a human corti-cotropic cell adenoma concur with in vivo findings of incomplete autonomy of secretion, parallel secretion of ACTH and LPH in response to provocative stimuli, and suppression by corticoste-roids. The technique has potential for exploring the cellular mechanisms controlling secretion by human corticotropic adenomas as well as the nature of the hormones produced.

^* This work was supported by the Cancer Research Campaign, Medical Research Council, University of London Central Research Fund, and the Smith, Kline, and French Foundation.

Received December 11, 1979.