Localization of Vasoactive Intestinal Polypeptide Receptor 1 (VPAC1) in Hypothalamic Neuroendocrine Oxytocin Neurons; A Potential Role in Circadian Prolactin Secretion.

Ida Stangerup,Jens Hannibal

doi:10.3389/fnana.2020.579466

Abstract

Prolactin (PRL) is a versatile hormone and serves a broad variety of physiological functions besides lactation. The release of PRL from lactotrophs in the pituitary has in rodents been shown to be released with a circadian pattern depending on the physiological state of the animal. The circadian release of PRL seems to be complex involving tonic inhibition by dopamine (DA) neurons on lactotrophs and one or even several releasing factors. Because of the circadian releasing pattern of PRL, neurons in the suprachiasmatic nucleus (SCN), “the brain clock,” and especially the neurons expressing neuropeptide vasoactive intestinal polypeptide (VIP), have been suggested to be involved in the circadian regulation of PRL. In the present study, we used fluorescence immunohistochemistry, in situ hybridization histochemistry, confocal microscopy, three-dimensional reconstruction, and highly specific antibodies to visualize the occurrence of VIP receptors 1 and 2 (VPAC1 and VPAC2) in mouse brain hypothalamic sections stained in combination with VIP, oxytocin (OXT), arginine vasopressin (AVP), and DA (tyrosine hydroxylase, TH). We demonstrated that VIP fibers most likely originating from the ventral part of the SCN project to OXT neurons in the magnocellular part of the paraventricular nucleus (PVN). In the PVN, VIP fibers were found in close apposition to OXT neuron exclusively expressing the VPAC1 receptor. Furthermore, we demonstrate that neither OXT neurons nor TH or AVP neurons were expressing the VPAC2 receptor. VPAC1 receptor expression was also found on blood vessels but not in neurons expressing AVP or TH. These findings suggest that VIP signaling from the SCN does not directly target DA neurons involved in PRL secretion. Furthermore, the findings support the notion that VIP from neurons in the SCN could regulate circadian release of OXT in the posterior pituitary or modulate OXT neurons as a releasing factor involved in the circadian regulation of PRL from pituitary lactotrophs.

Highlights

Prolactin (PRL) is an extremely versatile hormone with regulatory functions in the reproductive system, immune system, and during lactation (Freeman et al, 2000)
VPAC1 receptor expression was found on blood vessels but not in neurons expressing arginine vasopressin (AVP) or tyrosine hydroxylase (TH). These findings suggest that vasoactive intestinal polypeptide (VIP) signaling from the suprachiasmatic nucleus (SCN) does not directly target DA neurons involved in PRL secretion
Immunostaining of VPAC1 in the mouse hypothalamus reveals a different pattern of staining, depending on the methods used for visualization

Summary

Introduction

Prolactin (PRL) is an extremely versatile hormone with regulatory functions in the reproductive system, immune system, and during lactation (Freeman et al, 2000). One rhythm generated by the ovarian cycle results in an afternoon proestrus PRL surge every fourth to fifth day Both mating and artificial cervical stimulation have been shown to generate another PRL secretion rhythm—a circadian rhythm—with a nocturnal PRL surge in the morning and a diurnal PRL surge in the afternoon (Freeman et al, 2000; Egli et al, 2004; Bertram et al, 2010). PRL secretion is primarily circadian regulated with a peak in serum concentration at the transition zone between day and night (Esquifino et al, 2004)

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Conclusion