1.Simultaneous Measurement of Serum Chemical Castration Agents and Testosterone Levels Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
Ko DH1, Lee K2, Jeon SH3, Song SH4, Yun YM5, Chun S1, Kim HS6, Kim JY6, In MK6, Song J7. J Anal Toxicol. 2016 Mar 17. pii: bkw017. [Epub ahead of print]
Chemical castration involves administration of drugs to prevent pathological sexual behavior, reduce abnormal sexual drive and treat hormone-dependent cancers. Various drugs have been used for chemical castration; however, substantial interindividual variability and side effects are often observed. In this study, we proposed a useful monitoring method for the application of chemical castration agents using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS). Testosterone, cyproterone acetate, medroxyprogesterone, goserelin acetate, leuprolide acetate and triptorelin acetate were analyzed by UPLC-MS-MS. The target drugs were extracted from serum samples by double protein precipitation using methanol. Testosterone-1,2-d2 and buserelin acetate were used as internal standards. Parameters of analytical performance were evaluated, including imprecision, linearity, ion suppression and detection capabilities. Testosterone measurements were compared with the results of immunoassays.
2.Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.
Jiang Q1, Lian A2, He Q2. Comp Biochem Physiol A Mol Integr Physiol. 2016 Jul;197:35-42. doi: 10.1016/j.cbpa.2016.03.008. Epub 2016 Mar 10.
Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect.
3.Sodium selenite supplementation does not fully restore oxidative stress-induced deiodinase dysfunction: Implications for the nonthyroidal illness syndrome.
Wajner SM1, Rohenkohl HC1, Serrano T1, Maia AL2. Redox Biol. 2015 Dec;6:436-45. doi: 10.1016/j.redox.2015.09.002. Epub 2015 Sep 9.
Nonthyroidal illness syndrome (NTIS) is marked by low T3 and high reverse T3 levels. The physiopathology is poorly understood but involves oxidative stress-induced disruption of the iodothyronine deiodinases, which activate or inactivate thyroid hormones. Selenium, an essential trace element, exerts antioxidant function mainly through the thioredoxin reductase (TRx) and glutathione peroxidase (GPx) redox-regulating systems. We evaluated the effect of sodium selenite on IL6-induced disruption on deiodinase function. Cell lines expressing endogenous deiodinases type 1(D1), 2(D2) or 3(D3) (HepG2, MSTO, and MCF-7 cells, respectively) were used in an intact cell model that mimics the deiodination process under physiological conditions of substrate and cofactor, in the presence or not of IL6, with or without selenite. Deiodinase activity was quantified by the amount of iodine-125 in the medium (D1 and D2) or by ion-exchange chromatography (D3).
4.Extended access to methamphetamine self-administration up-regulates dopamine transporter levels 72 hours after withdrawal in rats.
D'Arcy C1, Luevano JE1, Miranda-Arango M1, Pipkin JA2, Jackson JA2, Castañeda E2, Gosselink KL1, O'Dell LE3. Behav Brain Res. 2016 Jan 1;296:125-8. doi: 10.1016/j.bbr.2015.09.010. Epub 2015 Sep 12.
Previous studies have demonstrated that there are persistent changes in dopamine systems following withdrawal from methamphetamine (METH). This study examined changes in striatal dopamine transporter (DAT), tyrosine hydroxylase (TH) and dopamine receptor 2 (D2) 72 h after withdrawal from METH intravenous self- administration (IVSA). Rats were given limited (1h) or extended (6h) access to METH IVSA (0.05 mg/kg/0.1 ml infusion) for 22 days. Controls did not receive METH IVSA. The rats given extended access to IVSA displayed higher METH intake during the first hour of drug access compared to rats given limited access. Extended access to METH also produced a concomitant increase in striatal DAT levels relative to drug-naïve controls. There were no changes in TH or D2 levels across groups. Previous studies have reported a decrease in striatal DAT levels during protracted periods (>7 days) of withdrawal from METH IVSA. This study extends previous work by showing an increase in striatal DAT protein expression during an earlier time point of withdrawal from this drug.