An endogenous opioid system is present and modulates dna synthesis during fetal rat development

The endogenous opioid growth factor (OGF), [Met⁵]-enkephalin, and its receptor, zeta (ζ), have been shown to modulate postnatal rat development. To examine whether prenatal growth processes are governed by opioids, time-mated Sprague-Dawley rats were injected on day 20 of gestation (E20) with either 50 mg/kg naltrexone (NTX), an opioid receptor antagonist known to block receptors for 24 hr/day, or sterile water (CO); [ H]-thymidine was given every hr over a 3-hr period. Four hr post-drug injection, females were euthanized, fetuses removed and processed for autoradiography. The labeling index (LI) of the cerebrum, cerebellum, and spinal cord from NTX fetuses were 28% to 200% greater than CO. The LI of bone was elevated 35%, and epithelia from tongue and intestine of NTX rats were increased 19% and 63%, respectively, above CO. Similar effects on DNA synthesis were observed in organs of E20 animals placed in culture. OGF and the Çreceptor also were detected in these organs at E20 by immunocytochemistry. These data suggest that an endogenous opioid system is present and functions by a tonic and direct inhibitory manner in ectodermal, mesodermal, and endodermal derivatives during prenatal development of the rat.