Growth hormone inhibitory and stimulatory actions of l-dopa in patients with acromegaly

Abstract

It is not clear whether dopamine (DA) has a central stimulating activity on GH secretion in patients with acromegaly, as it does in normal subjects. To clarify this, we compared the GH inhibitory potencies of DA, which does not cross the blood-brain barrier (BBB), and l-dopa or bromocriptine, which do cross the BBB, in 23 patients with acromegaly. Further, we examined the central effects of l-dopa after selectively blocking peripheral (median eminence and pituitary) DA receptors with domperidone (a DA D2 receptor blocker which does not cross the BBB). After the administration of DA (5 μg/kg.min, iv, for 90 min), l-dopa (500 mg, orally), or bromocriptine (2.5 mg, orally), the mean plasma GH decrease was greatest after DA [maximum decrement, 71.9 ± 3.8% (±sem); n = 21] compared to l-dopa (44.1 ± 5.6%; n = 23; p < 0.001) or bromocriptine (58.9 ± 5.0%; n = 20; p < 0.02). Eleven of these patients received a single infusion of domperidone (0.22 mg/min, iv, for 180 min) or a combination of domperidone and l-dopa. Mean plasma GH levels did not change during domperidone alone. However, plasma GH levels in these patients increased significantly when l-dopa was administered 30 min after the start of domperidone infusion (vs. control study: at 90 min, 137.3 ± 10.8% vs. 100.2 ± 3.9%, p < 0.01; at 120 min, 138.8 ± 19.7% vs. 106.5 ± 3.1%, p < 0.05). In contrast, one patient who had a distinct plasma GH increase in response to the domperidone-l-dopa test had no increase in plasma GH when given l-dopa 30 min after the start of a sulpiride infusion (DA D2 receptor blocker which crosses the BBB; 1.1 mg/min, iv, for 180 min). Unlike GH, plasma PRL responses to domperidone infusion were not modified by the additional administration of l-dopa. These results suggest that in acromegaly, DA has not only direct suppressive effects on the pituitary tumor somatotrophs, but also indirect stimulatory effects via the hypothalamus; therefore, the hypothalamic GH-releasing system is not entirely suppressed by excessive tumor GH secretion. © 1987 by The Endocrine Society.