Opioidergic regulation of thyroid activity: possible interference with the serotonergic system

Acute systemic administration of (D-Met2, pro5-NH2)-enkephalin (ENKamide), a very potent enkephalin analog, and of morphine not only diminished the basal levels of serum TSH under resting conditions, but also significantly reduced the enhanced serum TSH concentrations induced by goitrogen treatment or by bilateral thyroidectomy. Acute administration of opiates failed to inhibit the pituitary TSH response to exogenous TRH administration. The TSH release-inhibiting effect of ENKamide was reversed by pretreatment with the serotonin synthesis inhibitor, para-chlorophenylalanine (pCPA) or with the central serotonin receptor blocker, metergoline. These results furnish evidence in favour of the following concepts: (a) opioid compounds equally influence the tonic release of the TRH-TSH system under resting conditions, and also suppress the reactive changes of this circuit following specific loads, leading to an activation of this system; (b) opioids do not act directly at the pituitary level in inhibiting TSH secretion, but rather seem to suppress the release of TRH from the hypothalamus; (c) they may exert their inhibitory effect on the activity of the TRH-TSH-thyroid system by increasing the activity of the central nervous serotonergic system.