The aim of the present study was to examine the role of nutritional status, the metabolic hormone ghrelin and their interrelationships in the control of chicken hormones involved in the regulation of reproduction. For this purpose, we identified the effect of food deprivation, administration of ghrelin 1-18 and their combination on plasma levels of testosterone (T), estradiol (E), arginine-vasotocin (AVT) and growth hormone (GH) as well as the release of these hormones by isolated and cultured ovarian fragments. It was observed that food deprivation reduces plasma T and E and increases plasma AVT and GH levels. Food restriction also reduced the amount of E produced by isolated ovaries, but it did not affect the ovarian secretion of T and AVT. No ovarian GH secretion was detected. Ghrelin administered to ad libitum fed chickens did not affect plasma T and E levels, but it did increase plasma GH and AVT concentrations. Moreover, it partially prevented the effect of food deprivation on plasma E and AVT levels, but not on T or GH levels. Ghrelin administration to control birds promoted ovarian T, but not E or AVT release and reduced T and no other hormonal outputs in birds subjected to food restriction. Our results (1) confirmed the ovarian origin of the main plasma T and E and the extra-ovarian origin of the main blood AVT and GH; (2) showed that food deprivation-induced suppression of reproduction may be caused by suppression of T and E and the promotion of AVT and GH release; (3) suggest the involvement of ghrelin in control chicken E, AVT and GH output; and (4) indicates that ghrelin can either mimic or modify the effect of the intake of low calories on chicken plasma and ovarian hormones, i.e. it can mediate the effect of metabolic state on hormones involved in the control of reproduction.
- MeSH
- Biomarkers blood MeSH
- Energy Metabolism physiology MeSH
- Estradiol blood MeSH
- Ghrelin pharmacology MeSH
- Chickens MeSH
- Ovary drug effects metabolism MeSH
- Food Deprivation physiology MeSH
- Growth Hormone blood MeSH
- Testosterone blood MeSH
- Vasotocin blood MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Entropy (ΔS), enthalpy (ΔH) and heat capacity (ΔCp) changes attending the oxytocin interaction with its two binding sites on myometrial cell membranes in sheep were derived from the temperature dependence of Kd values. The high affinity oxytocin site (Kd on the order of 10(-9)mol l(-1), 25 °C), ascribed to the oxytocin receptor (OXTR), is entropy-driven in the temperature range 0-37 °C. Enthalpy component prevails as a driving force in the binding to the low affinity site (Kd ≈ 10(-7)) within the higher temperature range. ΔCp values in both cases do not differ significantly from zero but become highly relevant in the presence of a GTP analog (10(-4)M GTP-γS). Under these conditions, ΔCp in the low site interaction becomes negative and ΔS is shifted toward negative values (enthalpy drift); ΔCp of the high affinity site rises to a high positive value and the interaction is even more strongly entropy driven. Atosiban, a competitive antagonist of oxytocin at OXTR displays a single significant binding site on myometrial cells (Kd about 10(-7)mol l(-1)). Thermodynamic profiles of atosiban and the low affinity oxytocin site show conspicuous similarities, indicating that the inhibitor is bound to the low affinity site, and not, with a lower affinity, to the putative receptor protein. It is suggested that the interaction of oxytocin with its responding system on myometrial membranes follows in two distinct steps that are likely to be associated with several independent binding domains in the GPCR receptor.
- MeSH
- Arginine Vasopressin metabolism MeSH
- Cell Membrane metabolism MeSH
- Myometrium metabolism MeSH
- Sheep MeSH
- Oxytocin metabolism MeSH
- Receptors, Oxytocin metabolism MeSH
- Temperature MeSH
- Thermodynamics MeSH
- Vasotocin analogs & derivatives metabolism MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Hexoprenaline MeSH
- Magnesium MeSH
- Humans MeSH
- Premature Birth drug therapy MeSH
- Ritodrine MeSH
- Pregnancy MeSH
- Tocolysis * contraindications adverse effects utilization MeSH
- Vasotocin analogs & derivatives administration & dosage MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Practice Guideline MeSH
- MeSH
- Betamethasone administration & dosage contraindications adverse effects MeSH
- Gestational Age MeSH
- Glucocorticoids administration & dosage contraindications MeSH
- Magnesium administration & dosage contraindications adverse effects MeSH
- Humans MeSH
- Premature Birth drug therapy MeSH
- Pregnancy MeSH
- Tocolytic Agents administration & dosage MeSH
- Vasotocin analogs & derivatives administration & dosage contraindications MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
OBJECTIVES: Oxytocin (OXY) in addition to peripheral actions has many central regulatory functions which can be studied on animal models. In the present study we examined in rats, which behavioral actions of OXY and long-acting carba-analog of OXY carbetocin (CBT) in the open-field can be inhibited by OXY-receptor antagonists. Our interest focused on the behavioral patterns considered indicative of anxiety-related behavior. To determine what is the participation of OXY receptor on OXY and CBT induced behavioral changes, we used two peptide and one nonpeptide OXY antagonists differing in selectivity for OXY receptor. METHODS: OXY, CBT as well as OXY antagonists were injected intraperitoneally, and spontaneous behavior (horizontal and vertical activity, grooming) of Wistar rats was observed in the circular open-field arena 60 min after application of drugs; in some experiments testing was performed without treatment few days after drug administration. RESULTS: OXY at the dose 0.05 mg/kg increased locomotion indicating anxiety attenuation, but 1.0 mg/kg reduced both locomotion and rearing. CBT in the dose range 0.1-3.0 mg/kg either did not change or increased horizontal activity. The increase in exploration after both peptides persisted for several days. A marked difference in the behavioral effects of the two peptides was grooming enhancement induced by OXY compared with the absence of this effect after CBT. The increase of the activity induced by OXY and CBT indicating anxiolytic-like action was blocked by OXY antagonists. However, the reduction of exploration induced by 1.0 mg dose of OXY was only partially reversed. The OXY induced enhanced grooming was completely antagonized by all used antagonists. CONCLUSIONS: Behavioral effects of OXY and its antagonists after their i.p. application indicate that they penetrate blood brain barrier. The diversity in potency of OXY antagonists to inhibit grooming and other behaviors induced by OXY suggests that receptors participating in these behaviors may differ in brain localization, receptor conformation and/or in the utilized signaling pathways.
- MeSH
- Analysis of Variance MeSH
- Hormone Antagonists pharmacology MeSH
- Behavior, Animal drug effects MeSH
- Restraint, Physical MeSH
- Stress, Physiological drug effects MeSH
- Camphanes pharmacology MeSH
- Rats MeSH
- Oxytocin analogs & derivatives administration & dosage MeSH
- Grooming drug effects MeSH
- Piperazines pharmacology MeSH
- Motor Activity drug effects MeSH
- Rats, Wistar MeSH
- Stress, Psychological drug therapy MeSH
- Receptors, Oxytocin antagonists & inhibitors MeSH
- Oxytocics administration & dosage MeSH
- Vasotocin analogs & derivatives pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
OBJECTIVE: To compare the efficacy and safety of atosiban and terbutaline for the inhibition of preterm labor. METHODS: Two hundred and forty-nine women diagnosed with preterm labor at 23-33 weeks of gestation were enrolled of whom 245 women received treatment, 116 with atosiban and 129 with terbutaline. At randomization, women were stratified by gestational age (< or =28 weeks and >28 weeks). Atosiban (iv bolus dose of 6.75 mg, then 300 microg/min for 3 h and 100 microg/min thereafter) and terbutaline (5-20 microg/min) were administered by iv infusion for 13-18 h. Re-treatment with study drug or an alternative tocolytic agent was allowed. Tocolytic effectiveness was assessed in terms of the number of women undelivered after 48 hours and 7 days and efficacy and tolerability in terms of the number of women remaining undelivered and not requiring alternative tocolytic therapy after 48 hours and 7 days of starting therapy. Safety was assessed in terms of maternal side effects and neonatal morbidity. RESULTS: Tocolytic effectiveness at 48 hours was 86.1% vs 85.3%; p=0.783, and after 7 days it was 76.5% vs 67.4%; p=0.067, in the atosiban and terbutaline groups, respectively. Tocolytic efficacy and tolerability after 48 hours was 72.2% vs 68.2%; p=0.51 and after 7 days was 55.6% vs 43.4%; p=0.08 in the atosiban and terbutaline groups, respectively. Overall, there were fewer clinically important adverse events with atosiban than with terbutaline. CONCLUSIONS: The efficacy of atosiban in the inhibition of preterm labor was shown to be comparable to terbutaline. Atosiban had a superior safety profile compared with terbutaline in terms of maternal and fetal adverse events, and comparable infant outcomes.
- MeSH
- Adrenergic beta-Agonists administration & dosage adverse effects therapeutic use MeSH
- Hormone Antagonists administration & dosage adverse effects therapeutic use MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Gestational Age MeSH
- Infusions, Intravenous MeSH
- Humans MeSH
- Oxytocin antagonists & inhibitors MeSH
- Obstetric Labor, Premature prevention & control MeSH
- Pregnancy MeSH
- Terbutaline administration & dosage adverse effects therapeutic use MeSH
- Tocolytic Agents administration & dosage adverse effects therapeutic use MeSH
- Vasotocin administration & dosage adverse effects analogs & derivatives therapeutic use MeSH
- Pregnancy Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Geographicals
- Czech Republic MeSH
- Denmark MeSH
- United Kingdom MeSH
- Sweden MeSH
