Interaction of L-dopa and GHRH on GH secretion in normal men

To determine how L-dopa stimulates GH secretion, we investigated its interaction with GHRH in vivo. Six normal men were studied on 4 occasions: 1) L-dopa-TRH: 500 mg L-dopa orally followed by 200 µg TRH 60 min later; 2) L-dopa-GHRH-TRH: 100 µg GHRH 1-44 iv 30 min after L-dopa followed by 200 µg TRH iv; 3) GHRH-TRH: 100 µg GHRH iv at 0 min, 30 min later 200 µg TRH iv; 4) TRH test: 200 µg TRH iv as a bolus. After L-dopa-TRH GH-levels increased significantly from 0.6 µg/l to 25.8 ± 9.6 (SE) µg/l at 60 min. Only a slight TSH and no PRL increase was observed after L-dopa-TRH. After L-dopa-GHRH-TRH the GH-increase was significantly higher (45.7 ± 11.1 µg/l) compared to L-dopa-TRH alone. GHRH-TRH increased GH-levels to 52.5 ± 12.1 µg/l, which was not significantly different from the GH-levels obtained when L-dopa-GHRH-TRH were given. TRH increased serum TSH and PRL to 6.3 ± 0.7 µU/ml and 715 ± 136 µU/ml, respectively, which was significantly higher compared to the TSH responses after L-dopa-TRH. The PRL and TSH increase after TRH only was also higher (TSH-max: 5.7 ± 0.5 µU/ml; PRL-max: 899 ± 154 µU/ml) compared to the TSH and PRL responses after L-dopa-TRH. Our results show that the combination of L-dopa with GHRH leads to the same GH response as GHRH only. However, both responses are significantly higher than the one after L-dopa alone. This observation indicates that the stimulatory effect of L-dopa on GH secretion is mediated by endogenous GHRH. The inhibition of the TSH and PRL response to TRH after L-dopa administration, however, is due to the direct action of the L-dopa metabolite dopamine on the anterior pituitary.