Role of endogenous opioids in progesterone antagonism on oestradiol-induced DNA synthesis in the rat uterus

To probe the possible involvement of endogenous opioid peptides (EOPs) in progesterone (PG) antagonism on oestradiol-17β-(OE) induced uterine cell proliferation, the opioid antagonist naltrexone hydrochloride (NTC) and anti-[Met⁵]-enkephalin antiserum (AME) were investigated for their effect on uterine DNA synthesis in ovariectomized rats pretreated with OE and PG 24 h before killing. An an index of DNA synthesis the rat of _vitro incorporation of [³H]thymidine ([³H]TdR) into DNA was measured. The inhibitory effect of PG on OE-induced DNA synthesis could be diminished by ∼ 42 and ∼ 20% by the NTX treatments given directly into the uterine horns 13 and 4 h before killing, respectively. Intraluminal AME treatments were only effective when they were administered 13 h before decapitation. Systemic blockade of opioid receptors by intraperitoneal NTX injections given every 6 h to the OE + PG-treated rats did not result in the disinhibition of uterine [³H]TdR incorporation. Our results suggest the involvement of EOPs-including [Met⁵]-enkephalin-as autocrine/paracrine factors in the PG antagonism on OE-induced uterine DNA synthesis.