Comparative Study of Human Fetal, Normal Adult, and Somatotropic Adenoma Pituitary Function in Tissue Culture*

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Abstract
Tissue from 14 somatotropic adenomas, 2 normal adult pituitaries, and 16 fetal pituitaries (10–20 weeks gestation) was maintained in culture for 2 weeks. The secretion of GH, PRL, LH, and TSH into culture medium was studied both in the basal state and in response to acute 3-h exposure to TRH, apomorphine, somatostatin (SRIF), LRH, and theophylline. The findings were compared with results of in vivo dynamic pituitary function tests performed in the adult patients before transsphe-noidal surgery. The adenoma tissue secreted 0.5 to more than 20 μg GH/ml culture medium-day; six adenomas also secreted measurable amounts of PRL. The normal adult pituitary tissue secreted significant amounts of all hormones measured. The fetal pituitaries also secreted all of the hormones, but PRL, TSH, and LH were barely detectable. Hormone release into culture medium declined rapidly in the first 3–4 days and then remained stable until the end of the culture period. TRH (2.8 × 10–6 M) inhibited GH secretion by fetal and normal adult pituitary tissue; in adenoma tissue from five acro-megalics who had shown paradoxical stimulation of GH by TRH in vivo, it caused significant stimulation in culture; in adenoma tissue from nine acromegalics who did not respond in vivo, TRH produced no effect in vitro. TRH stimulated PRL secretion from both normal adult and adenoma pituitary tissue but had no effect on PRL release by fetal pituitaries. Apomorphine (1.6 × 10–6 M) suppressed GH secretion from fetal and normal adult tissue as well as from adenoma tissue of acromegalics who had shown either a stimulation or a paradoxical suppression of GH in vivo; it had no significant effect on GH release from the tissue of patients who had shown no response in vivo. Apomorphine suppressed PRL secretion from normal adult and adenoma tissue; no effect could be shown on fetal pituitaries because of low basal secretion. SRIF (10–6 M) suppressed GH secretion from all normal adult and adenoma tissues studied; suppression of GH secretion from the fetal pituitary was reported previously (26). It also suppressed PRL secretion in adenoma and normal adult pituitary tissue. LRH (10–6 M) suppressed GH secretion from normal adult pituitaries and to a lesser degree from adenomas and fetal pituitary tissue; it suppressed PRL release from normal adult pituitaries but not from adenoma tissue. Theophylline (1 HIM) was studied in adenoma tissue only and caused significant stimulation of GH secretion. Several conclusions were reached. 1) TRH may be a physiological regulator of GH secretion. Its paradoxical effect in acromegaly appears to be caused by an alteration at the level of the tumor cell. 2) The direct effect of apomorphine on normal pituitary tissue is a suppression of both GH and PRL secretion; the paradoxical GH suppression observed in vivo in some acro-megalics is due to an alteration of the extrapituitary action(s) of apomorphine; on the other hand, nonresponsiveness to this dopaminergic agent seems to be caused by a change in the adenoma cell itself. 3) SRIF suppresses GH secretion from the normal pituitary and adenoma tissue in an identical manner. 4) The abnormalities observed in the adenomas generally do not appear to be a reversion toward the fetal state. (J Clin Endo-crinol Metab54: 6, 1982)

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