Lack of functional GABAB receptors alters GnRH physiology and sexual dimorphic expression of GnRH and GAD-67 in the brain
Lack of functional GABAB receptors alters GnRH physiology and sexual dimorphic expression of GnRH and GAD-67 in the brain
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DOI：
10.1152/ajpendo.00532.2009
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发表时间：
2010-03-01
影响因子：
5.1
通讯作者：
Lux-Lantos, Victoria A.
中科院分区：
文献类型：
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作者：
Catalano, Paolo N.;Di Giorgio, Noelia;Lux-Lantos, Victoria A.
Catalano PN，Di Giorgio N，Bonaventura MM，Bettler B，Libertun C，Lux-Lantos VA.功能性GABAB受体的缺乏改变了GnRH生理学以及GnRH和GAD-67在脑中的性二态表达。Am J Physiol Endocrinol Metab 298：E683-E696，2010.首次发表于2009年12月15日; doi：10.1152/ajpendo.00532.2009.- GABA是主要的抑制性神经递质，通过GABA（A/C）和GABA（B）受体（GABA（B）Rs）发挥作用;对促性腺激素调节至关重要。我们研究了在GABA（B1）敲除（GABA（B1）KO）小鼠中功能性GABA（B）受体的缺乏是否影响促性腺激素轴生理学。处死成年雄性和雌性GABA（B1）KO和野生型（WT）小鼠，收集血液和组织样本。采用放射免疫分析法测定大鼠下丘脑、嗅球和额顶叶皮质中促性腺激素释放激素（GnRH）的含量。通过实时定量PCR（qRT-PCR）评价了视前区-下丘脑前部（POA-AH）、下丘脑内侧基底后部（MBH-PH）、OB和CT中的GnRH表达。放免法测定下丘脑组织块脉冲式GnRH分泌。采用高效液相色谱法测定HT和CT中GABA、谷氨酸和牛磺酸的含量。通过qRT-PCR测量POA-AH、MBH-PH和CT中的谷氨酸脱羧酶-67（GAD-67）mRNA。促性腺激素含量，血清水平，腺垂体细胞培养物（ACC）的分泌物测定放射免疫法。与雌性动物相比，WT雄性动物POA-AH中GnRH mRNA表达增加;在GABA（B1）KO小鼠中，这种表达模式相反。MBH-PH、OB和CT没有遵循这种模式。在GABA（B1）KO雌性中，GnRH脉冲频率增加，GABA和谷氨酸含量增加。POA-AH GAD-67 mRNA在该区域的表达模式与GnRH mRNA相同。垂体促性腺激素含量和血清促性腺激素水平在基因型间无差异。在GABA（B1）KO雌性ACC中观察到基础LH分泌增加和GnRH刺激的促性腺激素反应降低。这些结果支持了这样的假设，即功能性GABABRs的缺乏改变了GnRH生理学，并严重影响了POA-AH中GnRH和GAD-67的性二态表达。
Catalano PN, Di Giorgio N, Bonaventura MM, Bettler B, Libertun C, Lux-Lantos VA. Lack of functional GABAB receptors alters GnRH physiology and sexual dimorphic expression of GnRH and GAD-67 in the brain. Am J Physiol Endocrinol Metab 298: E683-E696, 2010. First published December 15, 2009; doi:10.1152/ajpendo.00532.2009.-GABA, the main inhibitory neurotransmitter, acts through GABA(A/C) and GABA(B) receptors (GABA(B)Rs); it is critical for gonadotropin regulation. We studied whether the lack of functional GABA(B)Rs in GABA(B1) knockout (GABA(B1)KO) mice affected the gonadotropin axis physiology. Adult male and female GABA(B1)KO and wild-type (WT) mice were killed to collect blood and tissue samples. Gonadotropin-releasing hormone (GnRH) content in whole hypothalami (HT), olfactory bulbs (OB), and frontoparietal cortexes (CT) were determined (RIA). GnRH expression by quantitative real-time PCR (qRT-PCR) was evaluated in preoptic area-anterior hypothalamus (POA-AH), medial basalposterior hypothalamus (MBH-PH), OB, and CT. Pulsatile GnRH secretion from hypothalamic explants was measured by RIA. GABA, glutamate, and taurine contents in HT and CT were determined by HPLC. Glutamic acid decarboxylase-67 (GAD-67) mRNA was measured by qRT-PCR in POA-AH, MBH-PH, and CT. Gonadotropin content, serum levels, and secretion from adenohypophyseal cell cultures (ACC) were measured by RIA. GnRH mRNA expression was increased in POA-AH of WT males compared with females; this pattern of expression was inversed in GABA(B1)KO mice. MBH-PH, OB, and CT did not follow this pattern. In GABA(B1)KO females, GnRH pulse frequency was increased and GABA and glutamate contents were augmented. POA-AH GAD-67 mRNA showed the same expression pattern as GnRH mRNA in this area. Gonadotropin pituitary contents and serum levels showed no differences between genotypes. Increased basal LH secretion and decreased GnRH-stimulated gonadotropin response were observed in GABA(B1)KO female ACCs. These results support the hypothesis that the absence of functional GABABRs alters GnRH physiology and critically affects sexual dimorphic expression of GnRH and GAD-67 in POA-AH.