THE EFFECT OF DYNORPHIN ON PLACENTAL PULSATILE HUMAN CHORIONIC-GONADOTROPIN SECRETION INVITRO

Using in vitro methods we have studied the effect of dynorphin (DYN) a natural k opioid receptor ligand upon hCG secretion in the first trimester placenta. In superfusion, where we have recently reported that hCG secretion is episodic, we found that the addition of 1-min pulses of DYN had a significant stimulatory effect upon pulsatile hCG secretion. This effect was seen at concentrations of 10(-8) mol/L-10(-11) mol/L. Higher doses (10(-6) mol/L) and lower doses (10(-12) mol/L) were ineffective. A 10-min administration was more effective than the 1-min pulses. Prolonged administration (90 min) caused an initial increase in pulsatile hCG secretion which was followed by a decrease to control values. However, upon stopping the prolonged opiate administration there was a substantial increase in hCG secretion. The involvement of opioid receptors in mediating the effect of DYN on hCG release was demonstrated by using naloxone, an opioid receptor antagonist. Coadministration of DYN, 10(-11) mol/L, and naloxone, 10(-10) mol/L, reduced markedly the effect of DYN. This was followed by a delayed increase in hCG secretion. Furthermore, des-tyrosine-DYN, the nonopioid derivative of DYN was 1000 times less potent in stimulating hCG release than DYN. The involvement of DYN in physiological control of placental hCG secretion is suggested.