Interaction of thyrotrophin releasing hormone and the enkephalin analogue DAMME on pituitary hormone secretion.

SUMMARY Because TRH counteracts the inhibitory effect of opiate peptides on LH secretion in cultured cells from normal pituitaries, six normal postmenopausal women were studied to determine whether TRH interacts in vivo with opioid peptides in the regulation of pituitary hormone secretion. At two different times a constant 3 h infusion of either saline or TRH (5 μg/min) was initiated. At 60 min a 250 μg bolus of the opiate agonist peptide D-AIa2-MePhe4-metenkephalin-0-ol (DAMME) was injected in one of the two saline and TRH infusion tests. The four treatments, i.e. saline infusion alone, saline infusion with a DAMME bolus, TRH infusion alone; and TRH infusion with DAMME bolus were given at random with an interval of at least 7 d. Blood samples were taken every 15 min during the 3 h study. DAMME induced a significant fall (P < 0.05) in serum LH (from 35±8.5 to 18.3±5.1 mlU/ml) (mean±SEM) without significantly affecting FSH levels (from 29 ± 11.2 to 26.9 ± 12.4 mlU/ml). These changes were not antagonized by the continuous infusion of TRH. PRL had a monophasic response pattern to continuous isolated TRH infusion; the basal levels increased from 4.2 ± 1.2 to 24.5 ± 6.8 ng/ml at 30 min and then slowly decreased with a plateau from 90 min until the end of the study. DAMME administration at 60 min induced a significant second peak of PRL secretion (44±6.5 ng/ml) 30 min later (P < 005). Basal serum TSH levels increased progressively during the first 135 min of TRH infusion (from 2.4 ± 0.5 to 18.5 ± 5.2 μU/ml), and then remained stable until the end of treatment. DAMME induced an even more striking TSH response 30 min after its administration at 60 min (P < 0.05), which was later maintained. In the absence of TRH infusion, DAMME administration did not modify either PRL or TSH basal levels. GH values did not significantly change during saline or TRH infusion alone, nor after DAMME i.v. administration at 60 min in either test. These findings are against an antagonistic effect of TRH and opioid peptides on the regulation of pituitary hormones in postmenopausal women. DAMME potentiating activity on PRL and TSH stimulatory action of continuous TRH infusion is shown. Also confirmed is the inhibitory effect of DAMME on LH secretion in postmenopausal women. Some of these effects may at least partially be mediated by the opiate inhibition of dopamine secretion.