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Potentiation of the ACTH response to metyrapone by L-dopa in the monkey
Abstract:
The intravenous injection of L-Dopa (15 mg/kg) to monkeys (Macaca mulatta) failed to alter plasma concentrations of ACTH and of 11-deoxy-cortisol. When cortisol synthesis was blocked with iv metyrapone, potentiation of ACTH secretion by L-Dopa became apparent. Simultaneous injection of L-Dopa and metyrapone resulted in a marked increase in plasma ACTH from 93 +/- 18 pg/ml to 432 +/- 80 pg/ml, whereas plasma 11-deoxycortisol increased from 1.5 +/- 0.2 mug/100 ml to 14.6 +/- 1.0 mug/100 ml 90 min after treatment. Throughout the experiment the rise in ACTH and in 11-deoxycortisol following coadministration of L-Dopa and metyrapone was significantly (P less than 0.01) higher than that produced by metyrapone administration alone. The results suggest that acute administration of L-Dopa in monkeys enhances the response of ACTH to metyrapone. L-Dopa (or one of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of hypothalamic corticotropin regulatory factor(s) and thereby enhance the release of ACTH.
Insights
L-Dopa enhances adrenocorticotropic hormone (ACTH) secretion in monkeys when cortisol synthesis is blocked. This suggests L-Dopa may influence the hypothalamic-pituitary-adrenal axis via neurotransmitter systems.
Area of Science:
- Neuroendocrinology
- Pharmacology
- Primate Physiology
Background:
- The regulation of adrenocorticotropic hormone (ACTH) secretion is complex.
- L-Dopa is a precursor to dopamine and other catecholamines.
- The interaction between L-Dopa and the hypothalamic-pituitary-adrenal (HPA) axis requires further elucidation.
Purpose of the Study:
- To investigate the effect of L-Dopa on ACTH secretion in the presence and absence of cortisol synthesis inhibition.
- To determine if L-Dopa potentiates ACTH release under conditions of HPA axis stimulation.
Main Methods:
- Intravenous administration of L-Dopa (15 mg/kg) to Macaca mulatta monkeys.
- Measurement of plasma ACTH and 11-deoxycortisol concentrations.
- Inhibition of cortisol synthesis using intravenous metyrapone.
Main Results:
- L-Dopa alone did not alter plasma ACTH or 11-deoxycortisol levels.
- Co-administration of L-Dopa and metyrapone significantly increased plasma ACTH and 11-deoxycortisol compared to metyrapone alone.
- The potentiation of ACTH secretion by L-Dopa was evident when cortisol synthesis was blocked.
Conclusions:
- Acute L-Dopa administration enhances the ACTH response to metyrapone in monkeys.
- L-Dopa's effect may involve modulation of hypothalamic neurotransmitter systems (noradrenergic or dopaminergic) affecting corticotropin-releasing factors.
- This suggests a role for L-Dopa in modulating HPA axis activity.
