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

Persistent Link:
http://hdl.handle.net/10150/183834
Title:
EFFECTS OF PROLACTIN ON BIOCHEMICAL MARKERS OF HEPATIC PRENEOPLASIA IN THE RAT.
Author:
BUCKLEY, ARTHUR RALPH, JR.
Issue Date:
1986
Publisher:
The University of Arizona.
Rights:
Copyright © 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.
Abstract:
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.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Prolactin.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Russell, Diane H.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleEFFECTS OF PROLACTIN ON BIOCHEMICAL MARKERS OF HEPATIC PRENEOPLASIA IN THE RAT.en_US
dc.creatorBUCKLEY, ARTHUR RALPH, JR.en_US
dc.contributor.authorBUCKLEY, ARTHUR RALPH, JR.en_US
dc.date.issued1986en_US
dc.publisherThe University of Arizona.en_US
dc.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.en_US
dc.description.abstractProlactin (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.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectProlactin.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRussell, Diane H.en_US
dc.contributor.committeememberSipes, I. Glennen_US
dc.contributor.committeememberPutnam, Charlesen_US
dc.contributor.committeememberBrendel, Klausen_US
dc.contributor.committeememberDavis, Thomasen_US
dc.identifier.proquest8623823en_US
dc.identifier.oclc697631300en_US
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