title: The effect of rivastigmine on the LPS-induced suppression of GnRH/LH secretion during the follicular phase of the estrous cycle in ewes.
abstract: This study was designed to determine the effect of a potent subcutaneously injected acetylcholinesterase inhibitor, rivastigmine (6mg/animal), on the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release during inflammation induced by an intravenous lipopolysaccharide (LPS) (400ng/kg) injection in ewes during the follicular phase of the estrous cycle. The results are expressed as the mean values from -2 to -0.5h before and +1 to +3h after treatment. Rivastigmine decreased the acetylcholinesterase concentration in the blood plasma from 176.9±9.5 to 99.3±15.1μmol/min/ml. Endotoxin suppressed LH (5.4±0.6ng/ml) and GnRH (4.6±0.4pg/ml) release; however, the rivastigmine injection restored the LH concentration (7.8±0.8ng/ml) to the control value (7.8±0.7ng/ml) and stimulated GnRH release (7.6±0.8pg/ml) compared to the control (5.9±0.4pg/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±8.0ng/ml) compared to the control group (9.0±5.4 and 21.3±3.5ng/ml). Rivastigmine also showed a moderating effect on cortisol and prolactin secretion (43.1±13.1 and 169.7±29.5ng/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.
authors.affiliation: Polish Academy of Sciences, The Kielanowski Institute of Animal Physiology and Nutrition, 05-110 Jabłonna, Poland. andrewherman@wp.pl
authors.forename: A P
authors.initials: AP
authors.lastname: Herman
authors.forename: A
authors.initials: A
authors.lastname: Krawczyńska
authors.forename: J
authors.initials: J
authors.lastname: Bochenek
authors.forename: K
authors.initials: K
authors.lastname: Haziak
authors.forename: K
authors.initials: K
authors.lastname: Romanowicz
authors.forename: T
authors.initials: T
authors.lastname: Misztal
authors.forename: H
authors.initials: H
authors.lastname: Antushevich
authors.forename: A
authors.initials: A
authors.lastname: Herman
authors.forename: D
authors.initials: D
authors.lastname: Tomaszewska-Zaremba
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects; D030762:Estrous Cycle / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D007279:Injections, Subcutaneous; D008070:Lipopolysaccharides; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D048448:Phenylcarbamates / Q000008:administration & dosage*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D000068836:Rivastigmine; D034561:Sheep, Domestic / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D002800:Cholinesterase Inhibitors; D008070:Lipopolysaccharides; D048448:Phenylcarbamates; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D000110:Acetylcholinesterase; D000068836:Rivastigmine