Giustina A, Brogan R, Conley L, Godi D, Manelli F, Wehrenberg W B
Department of Internal Medicine, University of Brescia, Italy.
Metabolism. 2000 Jun;49(6):778-83. doi: 10.1053/meta.2000.6259.
The secretion of growth hormone (GH) in both male and female rats is controlled by two main neuropeptides, GH-releasing hormone (GHRH), which is stimulatory, and somatostatin, which is inhibitory. Recently, it has been shown that galanin (GAL) also stimulates GH secretion, although the underlying mechanism is still unknown. It was the aim of this study to begin to elucidate if and how GAL regulates its own production at the hypothalamic and pituitary level. Rats underwent the following experimental trials. In experiment 1, adult male and female rats had blood samples collected at -15 minutes, -7.5 minutes, and immediately preceding a subcutaneous (s.c.) injection of GAL at a dose of either 50 or 200 microg/kg. Blood samples were collected at 5, 10, 15, 30, and 60 minutes, and the GH concentration was measured using a radioimmunoassay. The tissues were collected and analyzed for mRNA levels of hypothalamic and pituitary GAL. In experiment 2, adult male and female rats were treated long-term with 200 microg/kg GAL for 7 days s.c., and the pituitary and hypothalamus were analyzed for GAL mRNA. Serum GH concentrations were significantly increased in acutely dosed male and female rats regardless of the dosage level. For the male and female animals acutely dosed with both 50 and 200 microg/kg GAL, hypothalamic GAL mRNA was decreased, whereas pituitary GAL mRNA was affected by 200 microg/kg GAL only in females (increased). For the animals treated long-term with GAL, hypothalamic GAL mRNA was decreased while mRNA for pituitary GAL was increased. We conclude that regardless of the dosage and duration of treatment, administration of GAL negatively regulates hypothalamic GAL mRNA in a non-gender-specific way. Pituitary GAL synthesis appears to be stimulated particularly during chronic SCGAL administration.
雄性和雌性大鼠体内生长激素(GH)的分泌受两种主要神经肽的控制,即具有刺激作用的生长激素释放激素(GHRH)和具有抑制作用的生长抑素。最近研究表明,甘丙肽(GAL)也能刺激GH分泌,但其潜在机制尚不清楚。本研究的目的是开始阐明GAL是否以及如何在下丘脑和垂体水平调节其自身的产生。大鼠接受了以下实验。在实验1中,成年雄性和雌性大鼠在皮下注射(s.c.)剂量为50或200μg/kg的GAL前15分钟、7.5分钟和即将注射时采集血样。在注射后5、10、15、30和60分钟采集血样,采用放射免疫分析法测定GH浓度。收集组织并分析下丘脑和垂体GAL的mRNA水平。在实验2中,成年雄性和雌性大鼠长期皮下注射200μg/kg GAL,持续7天,分析垂体和下丘脑的GAL mRNA。无论剂量水平如何,急性给药的雄性和雌性大鼠血清GH浓度均显著升高。对于急性注射50和200μg/kg GAL的雄性和雌性动物,下丘脑GAL mRNA减少,而垂体GAL mRNA仅在雌性动物中受200μg/kg GAL影响(增加)。对于长期接受GAL治疗的动物,下丘脑GAL mRNA减少,而垂体GAL mRNA增加。我们得出结论,无论治疗剂量和持续时间如何,GAL的给药均以非性别特异性方式对下丘脑GAL mRNA产生负调节作用。垂体GAL合成似乎在慢性皮下注射GAL期间尤其受到刺激。