Prolactin promotes normal liver growth, survival, and regeneration in rodents: effects on hepatic IL-6, suppressor of cytokine signaling-3, and angiogenesis.
Prolactin (PRL) is a potent liver mitogen and proangiogenic hormone. Here, we used hyperprolactinemic rats and PRL receptor-null mice (PRLR(-/-)) to study the effect of PRL on liver growth and angiogenesis before and after partial hepatectomy (PH). Liver-to-body weight ratio (LBW), hepatocyte and sinusoidal endothelial cell (SEC) proliferation, and hepatic expression of VEGF were measured before and after PH in hyperprolactinemic rats, generated by placing two anterior pituitary glands (AP) under the kidney capsule. Also, LBW and hepatic expression of IL-6, as well as suppressor of cytokine signaling-3 (SOCS-3), were evaluated in wild-type and PRLR(-/-) mice before and after PH. Hyperprolactinemia increased the LBW, the proliferation of hepatocytes and SECs, and VEGF hepatic expression. Also, liver regeneration was increased in AP-grafted rats and was accompanied by elevated hepatocyte and SEC proliferation, and VEGF expression compared with nongrafted controls. Lowering circulating PRL levels with CB-154, an inhibitor of AP PRL secretion, prevented AP-induced stimulation of liver growth. Relative to wild-type animals, PRLR(-/-) mice had smaller livers, and soon after PH, they displayed an approximately twofold increased mortality and elevated and reduced hepatic IL-6 and SOCS-3 expression, respectively. However, liver regeneration was improved in surviving PRLR(-/-) mice. PRL stimulates normal liver growth, promotes survival, and regulates liver regeneration by mechanisms that may include hepatic downregulation of IL-6 and upregulation of SOCS-3, increased hepatocyte proliferation, and angiogenesis. PRL contributes to physiological liver growth and has potential clinical utility for ensuring survival and regulating liver mass in diseases, injuries, or surgery of the liver.
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México;
Bibiana
B
Moreno-Carranza
Maite
M
Goya-Arce
Claudia
C
Vega
Norma
N
Adán
Jakob
J
Triebel
Fernando
F
López-Barrera
Andrés
A
Quintanar-Stéphano
Nadine
N
Binart
Gonzalo
G
Martínez de la Escalera
Carmen
C
Clapp
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006498:Hepatectomy; D006966:Hyperprolactinemia / Q000097:blood* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D010903:Pituitary Gland, Anterior / Q000378:metabolism / Q000637:transplantation; D011388:Prolactin / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015850:Interleukin-6; D011981:Receptors, Prolactin; C491411:Socs3 protein, mouse; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C467498:vascular endothelial growth factor A, rat; D011388:Prolactin
interleukin-6; liver angiogenesis; liver growth and regeneration; prolactin; suppressor of cytokine signaling-3; vascular endothelial growth factor