Prolactin protects cardiomyocytes against intermittent hypoxia-induced cell damage by the modulation of signaling pathways related to cardiac hypertrophy and proliferation.

OBJECTIVES

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.

METHOD AND

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.