Inhibitory influence of thyrotropin releasing hormone administration on growth hormone response to low doses of growth hormone-releasing hormone in normal man

Literature data show that TRH may have either stimulatory or inhibitory actions on GH release according to pathophysiological conditions of the subject. In view of this dual effect of TRH, we studied the possible interaction of TRH and GRF on GH secretion. Six healthy male volunteers received iv in different occasions and in random order: 1 ) GRF 0.05 µg/Kg; 2) GRF 0.1 µg/Kg; 3) GRF 1 µg/Kg; 4) GRF 0.05 µg/Kg + TRH 400 µg, simultaneously; 5) GRF 0.05 µg/Kg + TRH 20 µg, simultaneously; 6) GRF 1 µg/Kg + TRH 400 µg, simultaneously, 7) the vehicle as control treatment. Blood samples were obtained at several time intervals and plasma GH, PRL and TSH were measured by RIA methods. Plasma GH significantly increased in all subjects after all the tested doses of GRF and after the combination of the highest and of the lowest doses of GRF + TRH (treatments 6 and 5). GH responses increased progressively with the dose of GRF administered, even if a clear dose-response relationship could not be demonstrated, owing to the considerable interindividual variability in the responsiveness. The administration of GRF 0.05 µg/Kg increased significantly plasma GH levels vs control treatment. The simultaneous administration of a low effective dose of GRF (0.05 µg/kg) plus a high dose of TRH (400 µg) was able to significantly inhibit the GH secretion elicited by GRF 0.05 µg/Kg alone. The other GRF + TRH combinations tested (treatments 5 and 6) did not modify the GH response to the same doses of GRF given alone. Plasma PRL and TSH did not change either after GRF at any dose or after the vehicle. The combination of GRF with TRH did not modify the normal responses of PRL and TSH to TRH alone. In conclusion, in normal subjects TRH is able to inhibit the GH response to low dose but not to high dose of GRF. These results show another type of interaction between the two hypothalamic hormones; from the practical point of view this interaction casts some doubts on the feasibility of the approach in combined testing of anterior pituitary reserve.