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-17 beta-(OE) induced uterine cell proliferation, the opioid antagonist naltrexone hydrochloride (NTX) 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. As an index of DNA synthesis the rate of in 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 approximately 42 and approximately 20% by the NTX treatments given directly into the uterine horns 13 and 4h 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.
Ordög
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Hungarian Academy of Science, Institute of Physiology, Pécs.
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Vértes
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D004723:Endorphins / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000276:immunology / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007116:Immunization, Passive; D009271:Naltrexone / Q000494:pharmacology; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D004723:Endorphins; D011374:Progesterone; D004958:Estradiol; D004744:Enkephalin, Methionine; D009271:Naltrexone; D004247:DNA