Effects of prenatal IL-6 exposure and hyperinsulinemia on neuroendocrine regulation

Abstract

Prenatal exposure to infection is associated with several neuroendocrine disorders. We therefore wanted to elucidate if cytokines, generated in response to maternal infection, play a key mechanistic role in this associations. The aim of this study was to examine the effect of prenatal IL-6 exposure, early and late of pregnancy, on blood pressure regulation, and renal and cognitive function in the adult offspring. Prenatal IL-6 exposure led to hypertension, in females at 5 wk of age, and males at 11 wk of age, dysregulation of the HPA-axis and the RAS system (in females), and altered renal fluid and electrolyte excretion. We also found neuron loss in the hippocampus with decreased learning performance in the morris water maze. These findings suggest that fetal IL-6 exposure reprograms the HPA-axis and RAS system, which results in hypertension and impaired learning ability at adult age. To conclude, these results show that prenatal IL-6 exposure can induce gender specific programming of neuroendocrine regulation with consequences in adult life.Hyperinsulinemi has been associated with left ventricle hypertrophy (LVH). Thus, theobjectives of this study were to investigate the effects of hyperinsulinemia on cardiac structure, function and gene expression, with control of counter-regulatory factors by adrenalectomy (ADX) and â-antagonist metoprolol (MET) treatment. Furthermore we wanted to investigate the effects on insulin signaling phosphatidylinositol 3 kinase (PI3K), and growth promoting- mitogen-activated protein kinases (MAPKs) pathways.Echocardiography performed after insulin treatment revealed LVH, with altered cardiac function (decreased cardiac output). Histochemical examination demonstrated myocyte hypertrophy and increases in interstitial fibrosis. Insulin also increased the activity of several regulatory genes important for growth, involved in adrenergic, angiotensin II, and the MAPK pathways. The insulin signaling pathway (PI3K) was on the other hand unaffected. In conclusion, our findings suggest that insulin has a direct trophic effect on the heart, via the MAPK pathway. These changes might be crucial for increased cardiovascular growth and fibrosis and signs of impaired LV function