TSH Release-Inhibiting Activity of Leucine-Enkephalin

Abstract

Since it is known that opiates inhibit TSH secretion, we felt it to be of interest to examine the effect of leucine-enkephalin on TSH secretion. When 250 µg leucine-enkephalin was injected i.p. into male rats, the mean serum TSH level at 30 minutes was 770 ng/ml as opposed to 1134 ng/ml in the saline control group (p < 0.02). To elucidate the mechanism of the TSH-inhibiting activity of leucine-enkephalin a series of in vitro experiments were undertaken with rat hemipituitaries. This system was first validated by demonstrating TSH-releasing activity of TRH at various times. The effect of leucine-enkephalin on TRH mediated TSH release was then determined. A suppressive effect was demonstrated (11.7 ± 0.9µg TSH/ hemipit./3 hours in the TRH alone group vs. 9.9 ± 0.8 µg TSH/hemipit./3 hours in the TRH plus leucine-enkephalin group, p ± 0.05). Naloxone failed to overcome the TSH-inhibiting activity of leucine-enkephalin (14.1 ± 1.2 µg TSH/ hemipit./3 hours for TRH alone vs. 9.0 ± 0.8 µg/hemipit./3 hours in the TRH plus leucine-enkephalin plus naloxone group, p< 0.005). In conclusion, leucine-enkephalin suppresses basal TSH in vitro and blocks the TSH response to TRH by a direct pituitary action. The possible physiological significance of these findings is discussed.