Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 112-141-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-138
Maite Goya-Arce*1, Fernando López-Barrera1, Jakob Triebel1, Nadine Binart2, Gonzalo Martinez de la Escalera1, Bibiana Moreno-Carranza1 and Carmen Clapp1
1National University of Mexico (UNAM), Querétaro, Mexico, 2INSERM Unit 693, Le Kremlin Bicetre, France
Interleukin-6 (IL-6) is an important mediator of hepatocyte proliferation, body homeostasis, and survival after partial hepatectomy (PH). Soon after PH, IL-6 improves liver regeneration and repair, but persistent IL-6 signaling promotes liver injury and death. PRL is a liver mitogen that increases in the circulation after PH and promotes liver regeneration. Given that PRL inhibits LPS-induced expression of IL-6 in hepatic Kupffer cells and stimulates the synthesis of the suppressor of cytokine signaling-3 (SOCS-3) in various cells, and that SOCS-3 can blunt IL-6 production and action in the liver, we hypothesized that PRL promotes liver regeneration through SOCS-3-mediated modulation of the detrimental effects of IL-6. Here, we investigated liver regeneration in PRL receptor-deficient mice (PRLR-/-) and analyzed the action of PRL on hepatic IL-6 and SOCS-3 production. Relative to wild-type animals, PRLR-/- mice subjected to 60% PH had smaller livers and displayed reduced survival between 24 and 48 hours after PH. Reduced survival could be linked to the upregulation of IL-6. At 3, 6, and 24 hours post-PH, PRLR-/- mice showed enhanced hepatic IL-6 mRNA levels that were associated with higher concentrations of serum IL-6 compared to PRLR+/+ animals. Moreover, the absence of the PRL receptor resulted in reduced expression of hepatic SOCS-3 at 3 and 6 hours after PH. Consistent with these results, we found that in rats, a 70% PH increases PRL circulating levels and that lowering these levels with CB-154, a dopamine receptor agonist that inhibits anterior pituitary PRL release, increases hepatic IL-6 expression and reduces SOCS-3 synthesis in the liver. In conclusion, we suggest that PRL promotes liver regeneration and survival via SOCS-3 inhibition of IL-6 and that this hormone has potential clinical utility for ensuring survival and increasing liver mass following injury.

Nothing to Disclose: MG, FL, JT, NB, GM, BM, CC

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: CONACyT grant 127496.