GABA对褪黑素降皮质酮作用的影响

<正> 在探索松果腺对下丘脑—垂体—肾上腺皮质轴的影响中,我们已经发现:切除松果腺使小鼠血清皮质酮升高,注射褪黑索则使其降低。为进一步分析这一过程的作用机制,本文重点研究下丘脑内γ氨基丁酸(GABA)所起的作用。实验用鼠龄4～5 wk昆明种小白鼠,用荧光法测定血清皮质酮,纸电泳一双波长薄层扫描法测定下丘脑GABA含量。1褪黑素对下丘脑CABA含量的影响45只小鼠,     

β-内啡肽抑制急性低氧暴露大鼠下丘脑促甲状腺素释放激素的释放(英文)

目的:研究β-内啡肽对急性低氧暴露下清醒大鼠下丘脑正中隆起和室旁核促甲状腺素释放激素(TRH)应答的影响.方法:放射免疫法测定脑组织TRH和血清T_3、T_4含量.雄性大鼠放置于低压舱中,模拟海拔7000米(8.2％ O_2),低氧暴露时间2 h.低氧暴露前,侧脑室注射β-内啡肽.结果:侧脑室分别注射β-内啡肽0.l和1μmol/L使低氧暴露大鼠下丘脑正中隆起TRH含量分别比生理盐水组[(4.8±0.3)μg/g蛋白]升高12％(P<0.05)和15％(P<0.0 5),室旁核TRH含量分别比生理盐水组[(180±21)ng/g蛋白]升高24％(P<0.05)和44％(P<0.01),血清 T_3、T_4浓度降低(P<0.05或P<0.01).纳洛酮10 μmol/L拮抗了 β-内啡肽0.1μmol/L对室旁核和正中隆起TRH含量升高以及血清T_3、T_4降低的效应.单独脑室注射纳洛酮10 μmol/L使下丘脑正中隆起和室旁核TRH减少(P<0.05或P<0.01),而血清T_3、T_4浓度升高(P<0.01).结论:β-内啡肽通过抑制正中隆起和室旁核TRH释放机制参与急性低氧暴露大鼠下丘脑TRH分泌的调节.     

低温时蛙皮素对IL-1β致热大鼠下丘脑和血浆cAMP含量的影响

目的以大鼠为实验对象建立发热动物模型,研究4℃时蛙皮素的降温作用及其与cAMP的关系。方法选择SD雄性大鼠,4℃下侧脑室微量注射蛙皮素、白细胞介素-1β,观察大鼠体温变化情况,并测定下丘脑和血浆中cAMP含量。结果在IL-1β诱导发热大鼠中,下丘脑及血浆中cAMP含量与对照组相比升高(P<0.01);蛙皮素可以降低大鼠正常体温,下丘脑cAMP含量与对照组相比亦随之降低(P<0.01);预先侧脑室注射蛙皮素能翻转大鼠IL-1β性发热,且下丘脑cAMP含量与IL-1β组相比明显下降(P<0.01)。结论4℃时蛙皮素能抑制IL-1β发热,其机制有可能是通过抑制cAMP合成或释放实现的。     

小鼠脑室内注射人参皂苷代谢物对脑室内注射应激诱导的血皮质酮水平变化的抑制

下丘脑-垂体-肾上腺轴(HPA)是与应激最密切相关的系统之一。曾发现脑室内注射人参总皂苷和人参皂苷Rc可降低因脑室内注射应激导致的血浆皮质酮水平的升高，2成分腹腔给药也可降低免疫应激引起的血浆皮质酮水平的升高，但人参皂苷主要肠内细胞代谢物20-O-β-D-吡喃葡糖基-20(5)-原人参萜二醇(化合物K)、     

探讨睾酮对大鼠癫痫发作的影响机制

目的 探讨睾酮对大鼠癫痫发作的影响机制.方法 应用反相高效液相色谱仪测定正常对照组(A组)、正常致痫组(B组)、阉割组(C组)、阉割致痫组(D组)、阉割后加小剂量睾酮致痫组(EL组)及阉割后加大剂量睾酮致痫组(EH>组)大鼠海马和皮质中谷氨酸(Gh)、天门冬氨酸(Asp)、γ-氨基丁酸(GABA)及甘氨酸(Gly)的含量变化.结果 各组大鼠海马氨基酸含量:D组Asp、Gh、Gly及GABA的含量较A、B及C组明显高,P<0.05.EL组和EH组Asp、Glu及GABA的含量较D组明显低,P<0.05.皮质:D组Asp、Glu及GABA的含量较A、B及C组明显高.P<0.05.EL和EH组Gh及GABA的含量较D组明显低,P<0.05.结论 睾酮的抗痫部分机制可能是由于其可使致痫大鼠脑组织内兴奋性氨基酸含量降低所致.     

“三棱-莪术”组分配伍对子宫肌瘤大鼠下丘脑和垂体激素的影响（英文）

目的:研究"三棱-莪术"组分配伍对子宫肌瘤大鼠下丘脑和垂体相关激素的影响。方法:将未生孕的SD雌性大鼠随机分为6组:正常对照组(NC),模型组(UL),桂枝茯苓胶囊组(GZFLC),"三棱-莪术"组分配伍高剂量组(HCRSR)、中剂量组(MCRSR)及低剂量组(LCRSR)。经肌注孕酮和灌胃己烯雌酚来诱导建立子宫肌瘤大鼠模型。经过五周的造模和药物治疗后,收集大鼠股动脉血、下丘脑及垂体,通过ELISA法测定血清,下丘脑和垂体中促性腺激素释放激素(GnRH),促卵泡激素(FSH)和促黄体激素(LH)的水平。结果:该造模方法成功地建立了大鼠子宫肌瘤模型。各组血清中GnRH,FSH和LH的浓度,以及下丘脑中的GnRH水平均无统计学意义(P 0.05)。模型组垂体中FSH和LH的表达高于正常组(P 0.01)。治疗后,高剂量(HCRSR)和桂枝茯苓胶囊组(GZFLC)组中"三棱-莪术"组分配伍的FSH和LH水平显著降低(P 0.01)。结论:这些数据表明"三棱-莪术"组分配伍可以降低子宫平滑肌瘤大鼠垂体中FSH和LH的表达。     

松果体和褪黑激素通过下丘脑影响大鼠腹腔巨噬细胞化学发光(英文)

目的:研究松果体和褪黑激素(Mel)是否通过下丘脑影响腹腔巨噬细胞功能.方法:松果体切除术;腹腔巨噬细胞化学发光测定;下丘脑地诺前列酮放射免疫测定;下丘脑注射Mel.结果:松果体切除后腹腔巨噬细胞化学发光值降低,下丘脑地诺前列酮含量升高,16:00 ip Mel(10 μg kg~(-1)d~(-1)×7d)可使其恢复,并升高正常大鼠腹腔巨噬细胞化学发光值,降低其下丘脑地诺前列酮含量.腹腔巨噬细胞化学发光值与下丘脑地诺前列酮含量的变化存在负相关(相关系数,r=-0.78,P<0.01).于下丘脑注射Mel 2μg,能提高正常大鼠和松果体切除大鼠腹腔巨噬细胞化学发光值.结论:下丘脑是松果体Mel影响腹腔巨噬细胞功能的主要作用部位之一.     

γ-氨基丁酸在围植入期小鼠子宫的含量及其意义

目的:通过检测γ-氨基丁酸(GABA)在围植入期第1日到第8日小鼠子宫的含量;并腹腔注射GABA,探讨其在围植入期小鼠子宫中的含量变化及对子宫蜕膜化的影响。方法:比色法检测妊娠小鼠第1日到第8日子宫中GABA含量;并于妊娠第5日开始腹腔注射GABA,浓度分别为0.05、0.5、5g/kg,每日1次,至第8日时称重蜕膜鼓包及石蜡切片后行HE染色,测量蜕膜化区域面积。结果:与第1日比较,第3日中GA-BA含量上调(P<0.05),第4日时出现下降趋势,却在第5日植入位点处出现最大值(P<0.01),且第6到8日的非植入位点处GABA含量显著高于植入位点;体内实验发现,0.05g/kgGABA及5g/kg GABA可显著减少蜕膜鼓包数量,0.5g/kgGABA可显著降低蜕膜鼓包重量。同时,0.05g/kg GABA及0.5g/kg GABA可显著减少蜕膜化区域面积。结论:γ-氨基丁酸含量在围植入期小鼠子宫中呈现动态变化,并可能参与抑制妊娠小鼠子宫蜕膜化。     

甜菜碱对戊四氮致痫大鼠海马GABA、Glu影响的研究

目的:观察甜菜碱对癫痫大鼠海马γ-氨基丁酸(GABA)、谷氨酸(Glu)的影响。方法:将健康雄性Wistar大鼠随机分为正常对照组(腹腔注射生理盐水,1.0 mL生理盐水灌胃),癫痫组(腹腔注射戊四氮,1.0mL生理盐水灌胃),甜菜碱高、中、低浓度组(腹腔注射戊四氮,甜菜碱灌胃),丙戊酸钠组(腹腔注射戊四氮,丙戊酸钠灌胃),实验结束后在低温条件下迅速取脑,ELISA实验检测GABA与Glu含量的变化。结果:ELISA结果表明癫痫组γ-氨基丁酸的含量与正常对照组相比显著下降(P<0.01)。甜菜碱高、中浓度组γ-氨基丁酸的含量与癫痫组比较显著增高(P<0.01);癫痫组谷氨酸的含量与正常组比较显著增高(P<0.01),甜菜碱高中低浓度与癫痫组比较显著下降(P<0.01)。结论:甜菜碱可通过增加GABA,降低Glu从而起到较好的抗癫痫作用。     

坤宁安浓缩丸对PMS大鼠下丘脑ER及其mRNA表达的影响

目的从自然围绝经期综合征(PMS)的大鼠下丘脑入手,探讨坤宁安浓缩丸对雌二醇(E2)—雌激素受体(ER)—ERmRNA雌激素生物活性全过程的影响,揭示其防治PMS的作用机制,并为临床应用提供理论依据。方法建立自然PMS的动物模型,免疫组织化学与原位杂交法检测青年空白组(A组)、模型组(B组)、坤宁安低剂量组及高剂量组(C组、D组)、对照更年安组(E组)、对照倍美力组(F组)各实验组大鼠下丘脑ER、ERmRNA的变化;放射免疫法检测各实验组血清中E2、促性腺激素释放激素(GnRH)、卵泡刺激素(FSH)、黄体生成素(LH)等的变化。结果B组大鼠血清E2水平低于A组,血清中GnRH、FSH、LH等的水平则高于A组(P<0.01),性腺轴老化。C、D、E组大鼠血清E2、GnRH、FSH、LH水平与B组比较差异无统计学意义(P>0.05);F组血清E2水平与B组相比差异有统计学意义(P<0.01),并接近A组水平,血清GnRH、FSH、LH水平与B组比较差异无统计学意义(P>0.05)。与A组相比,B组下丘脑中ER、ERmRNA含量表达较弱(P<0.01);C、D、E组均能上调ER、ERmRNA在下丘脑组织中的表达,其中D组阳性表达最强,与B组相比差异有统计学意义(P<0.01);F组与B组相比差异无统计学意义(P>0.05)。结论坤宁安浓缩丸通过提高围绝经期大鼠下丘脑组织中ERmRNA的转录水平,使ER的合成增加,从而提高雌激素靶组织中ER的含量以增强雌激素的生物活性而发挥治疗作用。     

Changes in testicular and serum hormone concentrations in the male rat following treatment with m-dinitrobenzene

m-Dinitrobenzene (m-DNB)-induced testicular atrophy has been attributed to a direct effect upon the germinal epithelium. However, such degenerative changes in the germinal epithelium should induce shifts in the testicular hormonal milieu, which would in turn alter the hypothalamic-pituitary gonadal axis in general. This study evaluated the endocrine status of male rats (killed 3 hr, 24 hr, 1 week, and 2 weeks) following a single oral dose of m-DNB (32 mg m-DNB/kg). Serum and pituitary leuteinizing hormone, follicle-stimulating hormone (FSH), and protactin and hypothalamic gonadotropin-releasing hormone (GnRH) concentrations were determined. Testosterone and androgen-binding protein concentrations in serum, interstitial fluid, seminiferous tubule fluid, and caput epididymis were also determined. In vitro basal and hCG-stimulated testosterone release was determined in the decapsulated testis. Results of the present study indicate that pituitary hormone concentrations and hypothalamic GnRH were unaffected after a single oral dose of m-DNB. Serum FSH was elevated at 2 weeks. There was a transient decrease in serum testosterone at 24 hr, which returned to control values at 1 and 2 weeks. Interstitial fluid, seminiferous tubule fluid, and caput epididymal testosterone concentrations were increased at 1 and 2 weeks. Basal testosterone release in vitro was increased at 2 weeks, while hCG-stimulated testosterone release was increased at 1 and 2 weeks. Androgen-binding protein concentrations in serum and interstitial fluid were increased at 1 and 2 weeks. Androgen-binding protein was increased at 24 hr and 1 week in seminiferous tubule fluid, but returned to control concentrations by 2 weeks. However, the total tubular content of androgen-binding protein was dramatically decreased at 2 weeks. Androgen-binding protein in the caput epididymis was unaltered following m-DNB treatment. These data demonstrate that m-DNB exerts a direct effect on the testes and not through alterations in hypothalamic and pituitary control of gonadal function.     

Impact of the UV-B filter 4-(Methylbenzylidene)-camphor (4-MBC) during prenatal development in the neuroendocrine regulation of gonadal axis in male and female adult rats

4-(Methylbenzylidene)-camphor (4-MBC), a UV-B ray filter, is an endocrine disruptors (ED). Our goal was to study the effect of 4-MBC on the neuroendocrine parameters that regulate reproduction in adult female and male rats that received this disrupter during prenatal development. The 4-MBC was administered (sc) to female rats (FO) since pregnancy onset, in doses of 100 mg/kg every other day. The litters (F1) were sacrificed at 70 days to determine gonadotrophin serum levels and also GnRH and the amino acids glutamate, aspartate and GABA release from the hypothalamus. The male litter rats (F1) present at adult age a decrease in serum LH and FSH concentration and so also GnRH, excitatory amino acids and GABA hypothalamic secretion. The female litters (F1) rats present at adult age an increase in serum LH and FSH concentration, whereas hypothalamic GnRH release was not modified. In these animals a significant increase of hypothalamic aspartate release as well as GABA secretion decrease were observed. Glutamate secretion was not modified. All these changes were accompanied by an advance (3 days) on the vaginal opening in 4-MBC rats group. In conclusion, prenatal administration of 4-MBC disrupts the gonadal axis in a sexual dimorphic mode that could be connected with the physiological sexual differences in the development of gonadotrophin secretion hypothalamic control mechanisms.     

Effects of 5-Day Styrene Inhalation on Serum LH and Testosterone Levels and on Hypothalamic and Striatal Amino Acid Neurotransmitter Concentrations in Male Rats

The volatile chemical styrene may impair male fertility. Testicular testosterone (T) production is controlled by the hypothalamic/pituitary/gonadal axis. From the mediobasal hypothalamus (MBH), gonadotropin-releasing hormone (GnRH) is released, which stimulates luteinizing hormone (LH) secretion from the pituitary, which in turn enhances T production. GnRH release is controlled by glutamate (GLU) and gamma-aminobutyric acid (GABA). GLU and GABA neurons are regulated by T. Thus, reduced fertility of styrene-exposed male workers may result from altered GLU/GABA neurotransmission, causing insufficient GnRH, LH, and T secretion. Therefore, we compared LH and T levels of male rats that have inhaled styrene (0, 150, 500, 1500 ppm for 6 h on 5 consecutive days) to GLU and GABA concentrations in the MBH and striatum. Animals were killed directly following the last exposure (immediate group) or after 24 h (recovery group). No suppression of LH or T levels was observed after styrene inhalation. LH levels of the immediate groups with 500 or 1500 ppm exposure were slightly but signficantly elevated. Hypothalamic GLU and GABA concentrations remained unchanged. Increased striatal GABA concentrations were determined in recovery groups with 500 or 1500 ppm exposure. Striatal GLU concentrations remained unaffected. Thus, we demonstrate slightly increased LH and T levels in styrene-exposed male rats after inhalation of the two higher doses. This effect did not correlate with hypothalamic GLU and GABA concentrations. With the limitations inherent to any animal model, these data obtained from a 5-day exposure study with rats suggest, but do not unequivocally prove, that styrene may have also no reproductive toxicity effects in men chronically exposed to this chemical.     

Effects of 5-day styrene inhalation on serum LH and testosterone levels and on hypothalamic and striatal amino acid neurotransmitter concentrations in male rats

The volatile chemical styrene may impair male fertility. Testicular testosterone (T) production is controlled by the hypothalamic/pituitary/gonadal axis. From the mediobasal hypothalamus (MBH), gonadotropin-releasing hormone (GnRH) is released, which stimulates luteinizing hormone (LH) secretion from the pituitary, which in turn enhances T production. GnRH release is controlled by glutamate (GLU) and gamma-aminobutyric acid (GABA). GLU and GABA neurons are regulated by T. Thus, reduced fertility of styrene-exposed male workers may result from altered GLU/GABA neurotransmission, causing insufficient GnRH, LH, and T secretion. Therefore, we compared LH and T levels of male rats that have inhaled styrene (0, 150, 500, 1500 ppm for 6 h on 5 consecutive days) to GLU and GABA concentrations in the MBH and striatum. Animals were killed directly following the last exposure (immediate group) or after 24 h (recovery group). No suppression of LH or T levels was observed after styrene inhalation. LH levels of the immediate groups with 500 or 1500 ppm exposure were slightly but significantly elevated. Hypothalamic GLU and GABA concentrations remained unchanged. Increased striatal GABA concentrations were determined in recovery groups with 500 or 1500 ppm exposure. Striatal GLU concentrations remained unaffected. Thus, we demonstrate slightly increased LH and T levels in styrene-exposed male rats after inhalation of the two higher doses. This effect did not correlate with hypothalamic GLU and GABA concentrations. With the limitations inherent to any animal model, these data obtained from a 5-day exposure study with rats suggest, but do not unequivocally prove, that styrene may have also no reproductive toxicity effects in men chronically exposed to this chemical.     

Effects of taurine,homotaurine and GABA on hypothalamic and striatal dopamine metabolism

Summary To elucidate the effects of taurine on hypothalamic and striatal dopaminergic neurotransmission we compared its effects to those of -aminobutyric acid (GABA) and homotaurine (a GABA_A-receptor agonist) on hypothalamic and striatal concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and, in the case of striatum, 3-methoxytyramine (3-MT) in rats. In addition, hypothalamic and striatal 5-hydroxytryptamine (5-HT) und 5-hydroxyindoleacetic acid, hypothalamic noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycol sulfate, and pituitary DA concentrations were also measured. The amino acids were injected into the lateral brain ventricles of conscious male rats in doses of 10 and 36 mol/rat, and rat were sacrificed 15 and 60 min later, respectively.Homotaurine (by 11010) but not the other two amino acids elevated striatal DA, whereas hypothalamic DA was increased by both taurine (36%) and homotaurine (31%). All three amino acids at 36 mol elevated striatal DOPAC, homotaurine (51%) more than taurine (31%) or GABA (30%), and hypothalamic DOPAC, both taurine (102%) and homotaurine (82%) clearly more than GABA (34%). Neither striatal nor hypothalamic HVA was altered by any of the amino acids. At 10 mol the amino acids decreased striatal 3-MT by about 40%. At 36 mol taurine and homotaurine reduced 3-MT by about 70%, whereas increasing the dose of GABA did not further reduce 3-MT. Both taurine and homotaurine at 36 mol decreased hypothalamic NA content. Neither hypothalamic nor striatal 5-HT metabolism was altered. In the neurointermediate lobe of the pituitary gland taurine at 10 mol but not at 36 mol slightly (20%) increased DA.These results show that taurine and homotaurine clearly alter the hypothalamic DA metabolism, and give further support to the suggestion that taurine and homotaurine similarly to GABA reduce the release of DA in the striatum. Homotaurine seems to alter the striatal DA metabolism more effectively than taurine or GABA. On the other hand, hypothalamic DA seems to be equally sensitive to taurine and homotaurine, and is clearly less sensitive to GABA. The pronounced elevation of hypothalamic DA and DOPAC after taurine and homotaurine could be related to changes in hypothalamic NA. Send offprint requests to L. Ahtee at the above address     

Altered regulation of pituitary gonadotropin-releasing hormone (GnRH) receptor number and pituitary responsiveness to GnRH in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases the potency of androgens as feedback inhibitors of luteinizing hormone (LH) secretion. Our objectives were to determine if this increase is due to pituitary or hypothalamic dysfunction (or both), and to investigate the mechanism by which TCDD produces this effect. Seven days after dosing, TCDD inhibited the compensatory increases in (i) pituitary gonadotropin-releasing hormone (GnRH) receptor number, (ii) LH secretory responsiveness of the pituitary to GnRH, and (iii) plasma LH concentrations which should have occurred in response to TCDD-induced decreases in plasma testosterone concentrations. TCDD did not inhibit these compensatory responses in the absence of testicular hormones, while treatment of castrated rats with testosterone restored the ability of TCDD to prevent these increases. These findings demonstrate that TCDD alters the androgenic regulation of pituitary GnRH receptor number and pituitary responsiveness to GnRH stimulation. The pituitary is therefore a target organ for TCDD; whether a hypothalamic defect is also involved in the altered regulation of LH secretion was not resolved. The compensatory increases in pituitary GnRH receptor number and plasma LH concentration elicited by low plasma testosterone concentrations were inhibited by similar doses of TCDD (ED50 20 micrograms TCDD/kg for both responses). We concluded that TCDD increases the potency of androgens as feedback inhibitors of LH secretion by increasing their potency as regulators of both pituitary GnRH receptor number and GnRH responsiveness. This is the first demonstration that TCDD treatment (i) affects pituitary responsiveness to a hormone secreted by a peripheral organ (testosterone), and (ii) alters the regulation of pituitary responsiveness to a hypothalamic hormone (GnRH).     

The release of inhibitory amino acids in the hypothalamus is tonically modified by impulses from aortic baroreceptors as a consequence of blood pressure fluctuations

We investigated in conscious, freely moving rats whether the release of GABA, taurine and arginine in the hypothalamus is influenced by impulses originating from peripheral baroreceptors. The posterior hypothalamic nucleus was superfused with artificial cerebrospinal fluid through a push-push cannula and the release of amino acids was determined in the hypothalamic superfusate of control rats, as well as of rats after bilateral aortic denervation (AD). AD led to hypertension and increased the lability of arterial pressure. In sham-operated rats, intravenous infusion of phenylephrine increased blood pressure and the hypothalamic release of GABA and taurine. AD almost abolished the phenylephrine-induced release of the inhibitory amino acids. Similarly, the pressor response to hypervolaemia, elicited by blood injection, enhanced the release rates of GABA and taurine only in sham-operated rats. Baroreceptor unloading evoked either by intravenous infusion of nitroprusside, or by haemorrhage, decreased the release rates of GABA and taurine in sham-operated rats but not in AD rats. Electrical stimulation of the afferent aortic depressor nerve enhanced extracellular GABA and taurine in the posterior hypothalamic nucleus. The release rate of arginine was not influenced by alterations in baroreceptor activity either in sham-operated or in AD rats. The findings support the idea that, in the hypothalamus,GABA and taurine are involved in central blood pressure regulation. The release of these two amino acids seems to be driven tonically by baroreceptor impulses. Moreover, the findings indicate that the baroreceptors of the aortic arch play a crucial role in the mediation of changes in hypothalamic GABA and taurine outflow so as to counteract blood pressure fluctuations. Received: 23 December 1996 / Accepted: 2 May 1997     

Effect of ethanol on GABA uptake and release from hypothalamic fragments

A study was performed on the effect of ethanol on the basal and K⁺-evoked efflux of endogenous GABA from rat hypothalamic fragments. The amount of GABA present in the medium and in the tissue was measured by radioreceptor assay. In vitro addition of ethanol (50 and 100 mM) enhanced the K⁺-evoked efflux of GABA in a Ca⁺⁺-dependent manner, and increased tissue GABA content. Since K⁺-evoked outflow induced by ethanol was not affected by the presence of nipecotic acid, ethanol appears to alter the uptake of endogenous GABA. An inhibitory effect of ethanol on ³H-GABA uptake was observed under K⁺ depolarization. On the other hand, acute ethanol administration produced a decrease in basal and K⁺-evoked efflux from hypothalamic fragments and in tissue GABA concentration. Changes in GABA efflux may lie behind some of the neuropharmacological effects of ethanol.     

The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173 receptor expressions in the female rat hypothalamic–pituitary–gonadal (HPG) axis

The recently discovered peptide phoenixin (PNX) and its receptor GPR173 are novel factors that exhibit a large spectrum of regulatory activity, especially when considered as a central modulator of GnRH‐related hormonal control of reproductive processes. It has been already proven that GnRH agonists and antagonists can modulate peptidergic signalling in the HPG axis. Despite these findings, there is so far no information regarding the influence of treatment with GnRH analogues on SMIM20/phoenixin signalling in the hypothalamic–pituitary–gonadal axis. In the current study, SMIM20/phoenixin and GPR173 mRNA levels were measured in the hypothalamus, pituitary and ovaries of female rats in the dioestrus phase following treatment with GnRH‐R agonist (buserelin) and antagonist (cetrorelix) using quantitative real‐time PCR. The serum PNX concentrations were also estimated with ELISA technique. The hypothalamic, hypophyseal and especially ovarian levels of SMIM20 mRNA were increased after both buserelin and cetrorelix administration. The GPR173 expressions were in turn decreased in the hypothalamus and pituitary. Treatment with the GnRH analogues led to the modulation of SMIM20/phoenixin and GPR173 mRNA expression in the female rat hypothalamic–pituitary–gonadal axis. By identifying buserelin and cetrorelix as novel modulators of phoenixin signalling in the animal HPG axis, these results cast new light on the GnRH analogues mode of action and contribute to a better understanding of the mechanisms responsible for the hormonal control of reproduction.