Central cholinergic signal-mediated neuroendocrine regulation of vasopressin and oxytocin in ovine fetuses

Lijun Shi,Fanxing Zeng,Zhice Xu,Yuying Zhang,Caiping Mao

doi:10.1186/1471-213x-8-95

Abstract

BackgroundThe hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli. It is well established that central cholinergic mechanisms are critical in the regulation of cardiovascular responses and maintenance of body fluid homeostasis in adults. Our recent study demonstrated that intracerebroventricular (i.c.v.) injection of carbachol elicited an increase of blood pressure in the near-term ovine fetuses. However, in utero development of brain cholinergic mechanisms in the regulation of the hypothalamic neuropeptides is largely unknown. This study investigated AVP and OT neural activation in the fetal hypothalamus induced by central carbachol.ResultsChronically prepared near-term ovine fetuses (0.9 gestation) received an i.c.v. carbachol (3 μg/kg). Fetal blood samples were collected for AVP and OT assay, and brains were used for c-fos mapping studies. I.c.v. carbachol significantly increased fetal plasma AVP and OT concentrations. Intense FOS immunoreactivity (FOS-ir) was observed in the fetal supraoptic nuclei (SON) and paraventricular nuclei (PVN) in the hypothalamus. Double labeling demonstrated that a number of AVP- and OT-containing neurons in the fetal SON and PVN were expressing c-fos in response to central carbachol.ConclusionThe results indicate that the central cholinergic mechanism is established and functional in the regulation of the hypothalamic neuropeptides during the final trimester of pregnancy. This provides evidence for a functional link between the development of central cholinergic mechanisms and hypothalamic neuropeptide systems in the fetus.

Highlights

The hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli
The finding that c-fos expression was induced in fetal AVP and OT neurons is the evidence that the hypothalamic pathway is activated and cholinergic mechanisms are functional in the control of fetal neuroendocrine function at 0.9 gestation
There are evidence regarding to neuroendocrinological responses induced by central cholinergic stimulation in adults, to our knowledge, whether central cholinergic mechanisms have developed in utero on the control of the neuropeptide release from the fetal hypothalamic-hypophysial system has been to date unknown

Summary

Introduction

The hypothalamic-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting arginine vasopressin (AVP) and oxytocin (OT) in response to a variety of signals, including osmotic and nonosmotic stimuli. Our recent study has shown that intracerebroventricular (i.c.v.) injection of carbachol produces reliable pressor responses [15] accompanied by a bradycardia in ovine fetuses at near-term Both nicotine and muscarinic receptors have been detected in the fetal brain [16,17,18,19,20]. Studies from other lines have shown that various signals, including angiotensin II, osmotic and hypovolemic stimulation, can induce AVP secretion and release from the hypothalamus and pituitary [21,22,23,24,25,26] The evidence from these two lines of research has independently proved that central cholinergic systems have developed in the last third of gestation, and the AVP system as a model of hypothalamic neuropeptide pathways has matured enough in prenatal neuroendocrine regulation. The present study was designed to fill the gap and build an initial link between these two lines of studies

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Conclusion