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

Chronically 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.The 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.The central nervous system (CNS) contains extensive cholinergic components [1], and central cholinergic pathways play an important role in the control of cardiovascular and body fluid homeostasis [2-6]. Carbachol, as a cholinergic agonist elicits a variety of neurobiological and physiological responses, including pressor responses, thirst, natriuresis as well as secretion and release of arginine vasopressin (AVP) in adult models [1,7-11].AVP and oxytocin (OT) are two major neuropeptides synthesized and released by magnocellular neurosecretory neurons in the hypothalamus. Both of them are involved in vascular functions and hydromineral homeostasis [12]. A variety of signals, including the central cholinergic stimulation, can cause release of AVP and OT in adults [13,14]. It is unknown however whether central cholinergic mechanisms have been developed in utero in the control of AVP and OT systems in the fetal hypothalamus. Addressing this question is important to both prenatal and postnatal health problems. Despite this, our recent study has shown that intracereb