title: Effects of atosiban on stress-related neuroendocrine factors.
abstract: Atosiban, an oxytocin/vasopressin receptor antagonist, is used to decrease preterm uterine activity. The risk of preterm delivery is undoubtedly associated with stress, but potential side effects of atosiban on neuroendocrine functions and stress-related pathways are mostly unknown. These studies were designed to test the hypothesis that the chronic treatment of rats with atosiban modulates neuroendocrine functions under stress conditions. Male rats were treated (osmotic minipumps) with atosiban (600 μg/kg per day) or vehicle and were restrained for 120 min/day for 14 days. All animals were treated with a marker of cell proliferation 5-bromo-2-deoxyuridine. Anxiety-like behavior was measured using an elevated plus-maze. Treatment with atosiban failed to modify plasma concentrations of the stress hormones ACTH and corticosterone, but led to a rise in circulating copeptin. Atosiban increased prolactin levels in the non-stressed group. Oxytocin receptor mRNA levels were increased in rats exposed to stress. Treatment with atosiban, in both control and stressed animals, resulted in a decrease in oxytocin receptor gene expression in the hypothalamus. No changes were observed in vasopressin receptor 1A and 1B gene expression. The decrease in hippocampal cell proliferation induced by stress exposure was not modified by atosiban treatment. This study provides the first data, to our knowledge, revealing the effect of atosiban on gene expression of oxytocin receptors in the brain. Atosiban-induced enhancement of plasma copeptin indicates an elevation in vasopressinergic tone with potential influence on water-electrolyte balance.
authors.affiliation: Laboratory of Pharmacological NeuroendocrinologyInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, SlovakiaDepartment of Pharmacology and ToxicologyFaculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, SlovakiaBiotechnology CenterNational Taiwan University, 50, Lane 155, Keelong Road, Section 3, Taipei, Taiwan.
authors.forename: S
authors.initials: S
authors.lastname: Babic
authors.affiliation: Laboratory of Pharmacological NeuroendocrinologyInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, SlovakiaDepartment of Pharmacology and ToxicologyFaculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, SlovakiaBiotechnology CenterNational Taiwan University, 50, Lane 155, Keelong Road, Section 3, Taipei, Taiwan.
authors.forename: M
authors.initials: M
authors.lastname: Pokusa
authors.affiliation: Laboratory of Pharmacological NeuroendocrinologyInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, SlovakiaDepartment of Pharmacology and ToxicologyFaculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, SlovakiaBiotechnology CenterNational Taiwan University, 50, Lane 155, Keelong Road, Section 3, Taipei, Taiwan Laboratory of Pharmacological NeuroendocrinologyInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, SlovakiaDepartment of Pharmacology and ToxicologyFaculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, SlovakiaBiotechnology CenterNational Taiwan University, 50, Lane 155, Keelong Road, Section 3, Taipei, Taiwan.
authors.forename: V
authors.initials: V
authors.lastname: Danevova
authors.affiliation: Laboratory of Pharmacological NeuroendocrinologyInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, SlovakiaDepartment of Pharmacology and ToxicologyFaculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, SlovakiaBiotechnology CenterNational Taiwan University, 50, Lane 155, Keelong Road, Section 3, Taipei, Taiwan.
authors.forename: S T
authors.initials: ST
authors.lastname: Ding
authors.affiliation: Laboratory of Pharmacological NeuroendocrinologyInstitute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 06 Bratislava, SlovakiaDepartment of Pharmacology and ToxicologyFaculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, SlovakiaBiotechnology CenterNational Taiwan University, 50, Lane 155, Keelong Road, Section 3, Taipei, Taiwan daniela.jezova@savba.sk.
authors.forename: D
authors.initials: D
authors.lastname: Jezova
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D015415:Biomarkers; D003345:Corticosterone / Q000097:blood*; D005786:Gene Expression Regulation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical / Q000009:adverse effects; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D006727:Hormone Antagonists; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; C047046:atosiban; D000324:Adrenocorticotropic Hormone; D014668:Vasotocin; D003345:Corticosterone
keywords: female reproduction; gene expression; hypothalamus; neuropeptides; receptors