The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion during the follicular phase of the estrous cycle in ewes

This study was designed to determine the effect of a potent subcutaneously injected acetylcholinesterase inhibitor, rivastigmine (6 mg/animal), on the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during inflammation induced by an intravenous lipopolysaccharide (LPS) (400 ng/kg) injection in ewes during the follicular phase of the estrous cycle. The results are expressed as the mean values from −2 to −0.5 h before and +1 to +3 h after treatment. Rivastigmine decreased the acetylcholinesterase concentration in the blood plasma from 176.9 ± 9.5 to 99.3 ± 15.1 μmol/min/ml. Endotoxin suppressed LH (5.4 ± 0.6 ng/ml) and GnRH (4.6 ± 0.4 pg/ml) release; however, the rivastigmine injection restored the LH concentration (7.8 ± 0.8 ng/ml) to the control value (7.8 ± 0.7 ng/ml) and stimulated GnRH release (7.6 ± 0.8 pg/ml) compared to the control (5.9 ± 0.4 pg/ml). Immune stress decreased expression of the GnRH gene and its receptor (GnRH-R) in the median eminence as well as LHβ and GnRH-R in the pituitary. In the case of the GnRH and LHβ genes, the suppressive effect of inflammation was negated by rivastigmine. LPS stimulated cortisol and prolactin release (71.1 ± 14.7 and 217.1 ± 8.0 ng/ml) compared to the control group (9.0 ± 5.4 and 21.3 ± 3.5 ng/ml). Rivastigmine also showed a moderating effect on cortisol and prolactin secretion (43.1 ± 13.1 and 169.7 ± 29.5 ng/ml). The present study shows that LPS-induced decreases in GnRH and LH can be reduced by the AChE inhibitor. This action of the AChE inhibitor could result from the suppression of pro-inflammatory cytokine release and the attenuation of the stress response. However, a direct stimulatory effect of ACh on GnRH/LH secretion should also be considered.