Prolactin's role in the early stages of liver regeneration in rats.
Liver regeneration after partial hepatectomy (PHx) is a complex process that is regulated by hemodynamic changes, the modulation of cytokines and growth factors, and the activation of immediate early transcription factors that lead to a round of hepatocyte mitosis. Among the factors involved, the pituitary hormone prolactin (PRL) has been shown to induce a hepatotrophic response after partial hepatectomy similar to that caused by phorbol esters; and in isolated hepatocytes PRL triggers a mitogenic response. However, it is becoming clear that PRL exerts a dual role acting in proliferation and differentiation processes. In this work, we have assessed the role of PRL in the early stages of liver regeneration in rats. To this end, three groups of rats were compared: Sham operated, regenerant and regenerant with PRL i.p. administration. Results show that PRL administration prior to partial hepatectomy caused an increase in the binding activity of several transcription factors involved in cell proliferation: AP-1, c-Jun and STAT-3, and in liver-specific differentiation and maintenance of energetic metabolism: CEBPalpha, HNF-1, HNF-4 at early time points and at later time points HNF-3. Hepatic sections show that PRL administration increases the number of proliferating cells within 5 h post-partial hepatectomy. The mRNA of the angiogenic and survival factors VEGF and HIF-1alpha, was also induced by PRL treatment. Data indicate that PRL triggers, either directly or indirectly, an acceleration of liver regeneration, preserving liver function and fulfilling a hepatoprotective role. J. Cell. Physiol. 219: 626-633, 2009. (c) 2009 Wiley-Liss, Inc.
Olazabal
Isabel M
IM
Departamento de Biología Molecular, Facultad de Ciencias C-V, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Muñoz
Jaime A
JA
Rodríguez-Navas
Carmen
C
Alvarez
Luis
L
Delgado-Baeza
Emilio
E
García-Ruiz
Josefa P
JP
D000818:Animals; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006498:Hepatectomy; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008115:Liver Regeneration / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011388:Prolactin / Q000008:administration & dosage / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D022763:CCAAT-Enhancer-Binding Protein-alpha; D017931:DNA Primers; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D011388:Prolactin; D048031:JNK Mitogen-Activated Protein Kinases