Effect of Central Injection of Neostigmine on the Bacterial Endotoxin Induced Suppression of GnRH/LH Secretion in Ewes during the Follicular Phase of the Estrous Cycle

Abstract

Induced by a bacterial infection, an immune/inflammatory challenge is a potent negative regulator of the reproduction process in females. The reduction of the synthesis of pro-inflammatory cytokine is considered as an effective strategy in the treatment of inflammatory induced neuroendocrine disorders. Therefore, the effect of direct administration of acetylcholinesterase inhibitor—neostigmine—into the third ventricle of the brain on the gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretions under basal and immune stress conditions was evaluated in this study. In the study, 24 adult, 2-years-old Blackhead ewes during the follicular phase of their estrous cycle were used. Immune stress was induced by the intravenous injection of LPS Escherichia coli in a dose of 400 ng/kg. Animals received an intracerebroventricular injection of neostigmine (1 mg/animal) 0.5 h before LPS/saline treatment. It was shown that central administration of neostigmine might prevent the inflammatory-dependent decrease of GnRH/LH secretion in ewes and it had a stimulatory effect on LH release. This central action of neostigmine is connected with its inhibitory action on local pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)α synthesis in the hypothalamus, which indicates the importance of this mediator in the inhibition of GnRH secretion during acute inflammation.

The Impact of Photoperiod on the Leptin Sensitivity and Course of Inflammation in the Anterior Pituitary

“…The ex vivo experiment conducted on the AP derived from sheep showed that LPS addition into a medium with explants collected from animals already treated with LPS significantly increased IL6 expression, which was not stated for explants derived from animals not treated with LPS [93]. Intracerebroventricular (icv) administration of LPS into the third ventricle increased the expression of IL6 in the ovine hypothalamic preoptic area during the reproductive season [94]. Further, IL1β injection into the third ventricular of the ovine brain caused a significant increase in IL6 and IL6ST expression in both photoperiods, while IL6R expression increased only during the short-day period at the level of the pineal gland [95].…”

“…TNFR2, as the opposite of TNFR1, may promote tissue repair and angiogenesis [102]. In ewes in the follicular phase of the estrous cycle, it was stated that the ICV injection of LPS increased TNF expression in the preoptic area of the hypothalamus [94]. On the other hand, a study conducted on the ovine AP explants showed no effect of LPS on TNF expression [93].…”

Acute Effect of Caffeine on the Synthesis of Pro-Inflammatory Cytokines in the Hypothalamus and Choroid Plexus during Endotoxin-Induced Inflammation in a Female Sheep Model

“…Studies on rats and sheep models indicated that both systemic LPS treatment and central administration of IL-1β, and TNFα into the region of the hypothalamus suppress the secretion of the gonadotropin-releasing hormone leading to downstream inhibition of the hypothalamic-pituitary-gonadal axis (HPG axis), the main neuroendocrine axis regulating reproduction [13,[16][17][18]. On the other hand, pharmacological inhibition of the synthesis of pro-inflammatory cytokines in the hypothalamus during endotoxin-induced immune challenge has been shown to reduce the inhibitory effect of inflammation on the activity of the HPG axis in sheep during the follicular phase [19].…”

The Effect of Photoperiodic Conditions on GnRH/LH Secretion in Ewes

“…Another factor influencing the HPG axis, whose secretion shows day/night fluctuations, is interleukin (IL)-1β [22]. Our previous studies showed that, acting at the level of hypothalamus, proinflammatory cytokines, particularly IL-1β, are potent negative regulators of GnRH secretion in ewes [58][59][60]. The study on rats showed that there are day/night changes in the hypothalamic IL-1β mRNA expression.…”