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EFFECTS OF PROLACTIN ON BIOCHEMICAL MARKERS OF HEPATIC PRENEOPLASIA IN THE RAT.

Prolactin (PRL) may be a key mammalian growth and developmental hormone. Hepatic receptors bind PRL implicating the liver as a PRL target. Recent evidence suggests that PRL triggers hepatic ornithine decarboxylase (ODC) induction, a marker of a trophic response. This suggests that in the liver PRL may contribute to neoplasia. To test this theory, PRL modulation of plasminogen activator (PA), DNA synthesis, cytochrome P450 (P450), liver hypertrophy and enzyme altered foci (EAF) was assessed. Cyclosporine, a PRL receptor antagonist, attenuated PRL-stimulated PA induction. PRL-stimulation of PA and ODC activity reflected age dependence. PRL administration to young rats stimulated hepatic microsomal P450 content 39% above control, an effect camparable to phenobarbital. Incubation of microsomes from PRL-treated rats with warfarin produced a metabolic pattern unique to PRL. PRL stimulated hepatic DNA synthesis up to 400%. This effect was shown to be specific for hepatic parenchymal cells. PRL for 6 weeks produced hepatic hypertrophy, an effect augmented by diethylnitrosamine (DEN). Additionally, incresed hepatic GGTase activity and EAF were demonstrated in rats treated with chronic PRL after DEN. Extrahepatic neoplasia was increased by partial hepatectomy PH and chronic PRL. PRL receptor coupling was investigated in PRL-dependent Nb₂ node lymphoma cells. ODC induction and proliferation were found to be coupled to protein kinase C (PKC) and calmodulin (CM) in experiments using pharmacological agents. Phosphatidylinositol (PI) turnover and ionic flux alterations were also implicated. These results suggest PRL receptor coupling to PI turnover and PKC activation in Nb₂ cells. PRL may be a key liver growth hormone. PRL induces PA, ODC and P450. Furthermore, its ability to promote EAF strongly implicates PRL in the ontogeny of hepatocarcinogenesis.

Identiferoai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/183834
Date January 1986
CreatorsBUCKLEY, ARTHUR RALPH, JR.
ContributorsRussell, Diane H., Sipes, I. Glenn, Putnam, Charles, Brendel, Klaus, Davis, Thomas
PublisherThe University of Arizona.
Source SetsUniversity of Arizona
LanguageEnglish
Detected LanguageEnglish
Typetext, Dissertation-Reproduction (electronic)
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.

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