Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle.

Andrzej P Herman,Dorota Tomaszewska-Zaremba,Karolina Wojtulewicz,Hanna Antushevich,Agata Krawczyńska,Janina Skipor,Anna Herman,Katarzyna Romanowicz,Joanna Bochenek,Kamila Paczesna

doi:10.1155/2017/6823209

Abstract

The study was designed to test the hypothesis that the inhibition of acetylcholinesterase (AChE) activity at the periphery by Neostigmine (0.5 mg/animal) will be sufficient to prevent inflammatory dependent suppression of the gonadotropin-releasing hormone (GnRH)/luteinising hormone (LH) secretion in ewes in the follicular phase of the estrous cycle, and this effect will be comparable with the systemic AChE inhibitor, Donepezil (2.5 mg/animal). An immune/inflammatory challenge was induced by peripheral administration of lipopolysaccharide (LPS; 400 ng/kg). Peripheral treatment with Donepezil and Neostigmine prevented the LPS-induced decrease (P < 0.05) in LHβ gene expression in the anterior pituitary gland (AP) and in LH release. Moreover, Donepezil completely abolished (P < 0.05) the suppressory effect of inflammation on GnRH synthesis in the preoptic area, when pretreatment with Neostigmine reduced (P < 0.05) the decrease in GnRH content in this hypothalamic structure. Moreover, administration of both AChE inhibitors diminished (P < 0.05) the inhibitory effect of LPS treatment on the expression of GnRH receptor in the AP. Our study shows that inflammatory dependent changes in the GnRH/LH secretion may be eliminated or reduced by AChE inhibitors suppressing inflammatory reaction only at the periphery such as Neostigmine, without the need for interfering in the central nervous system.

Highlights

An immune/inflammatory challenges caused by the bacterial or viral infection could be one of the reasons of reproductive disorders in both humans and animals [1]
The present study showed that peripheral AChE inhibitor, Neostigmine, the same as Donepezil, suppressed inhibitory effect of acute inflammation on luteinising hormone (LH) release and LHβ gene expression in the anterior pituitary gland (AP) in ewes during the follicular phase of the estrous cycle
The study supports the results of our previous experiment on ewes which showed that systemic AChE inhibitor successfully reduced negative effect of inflammation on LH secretion in the follicular phase ewes [13]

Summary

Introduction

An immune/inflammatory challenges caused by the bacterial or viral infection could be one of the reasons of reproductive disorders in both humans and animals [1]. It is postulated that the interaction between the immune and neuroendocrine systems may occur at all levels of the neurohormonal system of hypothalamic-pituitary-gonadal (HPG) axis controlling the female reproductive process. A important role in the communication between these two systems is played by the hypothalamus, the part of the brain responsible for the integration and processing of signals from the nervous, endocrine, and immune systems, what is essential for maintaining the homeostasis. The hypothalamus plays a key role in the control of reproduction in females by tonic release of gonadotropin-releasing hormone (GnRH) to the hypothalamic-pituitary portal circulation. It was previously reported that both acute and prolonged inflammation induced by peripheral administration of bacterial endotoxin-lipopolysaccharide (LPS) may disturb the secretion of GnRH and LH [3, 4]. The study on ewes in the follicular phase of the estrous cycle showed that inflammation interrupted the preovulatory estradiol increase and delayed

Methods

Results

Conclusion