title: Prolactin protects cardiomyocytes against intermittent hypoxia-induced cell damage by the modulation of signaling pathways related to cardiac hypertrophy and proliferation.
abstract: OBJECTIVE
  Prolactin (PRL) is a multifunctional hormone that influences multiple physiological processes. It has been shown to have a protective effect on the cardiovascular system; however, the mechanisms of this effect are poorly understood. The purpose of the study was to elucidate the role of PRL in intermittent hypoxia (IH)-induced apoptosis in the cardiovascular system.
  
  
  RESULTS
  We established a hyperprolactinemic rat model by implanting two anterior pituitary (AP) glands into the renal capsule of male Sprague-Dawley rats. The rats were kept under normoxic conditions for 4weeks after implantation in order to reach the expression plateau of PRL in the plasma, and then treated with IH for 7 or 14days. Their hearts were then removed for histological and protein expression analyses. Cerebral cortex (CX)-grafted control rats challenged with IH displayed unique phenotypes such as a thicker heart wall, an abnormal myocardial architecture and an increased interstitial space of the left ventricle. They exhibited reduced expressions of p-JAK2, p-STAT5, cell cycle-dependent proteins (cyclin D1, cyclin E and cyclin A), IGF-IRα, PI3Kα, p-AKT and p-ERK1/2 in cardiomyocytes at 7days.
  
  
  CONCLUSIONS
  Our comprehensive analysis suggested that high plasma PRL can protect rat cardiomyocytes against IH through (1) the p-JAK2 and p-STAT5 pathways for transient cell proliferation, (2) the PI3Kα/AKT and MAPK survival pathways through IGF-I, and (3) the downregulation of IGF-II and ERK5, which inhibit cell hypertrophy.
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
authors.forename: Dennis Jine-Yuan
authors.initials: DJ
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Division of Cardiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Peiying
authors.initials: P
authors.lastname: Pai
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Department of Physiology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shyi-Gang P
authors.initials: SG
authors.lastname: Wang
authors.affiliation: Athletic Training and Health Department, National Taiwan Sport University, Taoyuan 333, Taiwan.
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Tsai
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Li
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. Electronic address: cyhuang@mail.cmu.edu.tw.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000367:Age Factors; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011388:Prolactin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D011388:Prolactin
keywords: Apoptosis; Cardiomyocytes; Intermittent hypoxia; Normoxic; Prolactin