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首页> 外文期刊>Neuroendocrinology: International Journal for Basic and Clinical Studies on Neuroendocrine Relationships >Expression analysis of hypothalamic and pituitary components of the growth hormone axis in fasted and streptozotocin-treated neuropeptide Y (NPY)-intact (NPY+/+) and NPY-knockout (NPY-/-) mice.
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Expression analysis of hypothalamic and pituitary components of the growth hormone axis in fasted and streptozotocin-treated neuropeptide Y (NPY)-intact (NPY+/+) and NPY-knockout (NPY-/-) mice.

机译：在禁食和链脲佐菌素处理的神经肽Y（NPY）-完整（NPY + / +）和NPY-敲除（NPY-/-）小鼠中生长激素轴的下丘脑和垂体成分的表达分析。

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摘要

In the fasted and the streptozotocin (STZ)-induced diabetic male rat, hypothalamic growth hormone (GH)-releasing hormone (GHRH) mRNA levels, and pulsatile GH release are decreased. These changes are believed to be due to a rise in hypothalamic neuropeptide Y (NPY) that inhibits GHRH expression. To directly test if NPY is required for metabolic regulation of hypothalamic neuropeptides important in GH secretion, NPY, GHRH and somatostatin (SRIH) mRNA levels were determined in fasted (48 h) and STZ-treated wild-type (NPY(+/+)) and NPY-knockout (NPY(-/-)) mice by ribonuclease protection assay. In addition, pituitary receptor mRNA levels for GHRH (GHRH-R), ghrelin (GHS-R) and SRIH (sst2) were assessed by RT-PCR. Under fed conditions the GH axis of NPY(+/+) and NPY(-/-) did not differ. In the NPY(+/+) mouse, fasting resulted in a 23% weight loss and >250% increase in NPY mRNA accompanied by a significant reduction in both GHRH and SRIH mRNA. These changes were associated with increases in pituitary expression of GHRH-R and GHS-R and a concomitant suppression of sst2. In the NPY(-/-) mouse, fasting also resulted in a 23% weight loss and comparable changes in GHRH-R and sst2, but failed to alter GHRH, SRIH and GHS-R mRNA levels. Fasting resulted in an overall increase in circulating GH, which reached significance in the fasted NPY(-/-) mouse. Induction of diabetes in NPY(+/+) mice, using a single, high-dose, STZ injection (150 mg/kg), resulted in modest weight loss (5%), and a 158% increase NPY expression which was associated with reciprocal changes in pituitary GHS-R and sst2 expression, similar to that observed in the fasted state, but no change in hypothalamic GHRH or SRIF expression was observed. Induction of diabetes in NPY(+/+) and NPY(-/-) mice, using a multiple, low-dose, STZ paradigm (5 consecutive daily injections of 40 mg/kg), did not alter body weight, hypothalamic neuropeptide expression or pituitary receptor expression, with the exception that sst2 mRNA levels were suppressed and GH levels did rise in the NPY(-/-) mouse. These observations demonstrate that NPY is not required for basal regulation of the GH axis, but is required for fasting-induced suppression of GHRH and SRIH expression, as well as fasting-induced augmentation of pituitary GHS-R mRNA. In contrast to the rat, fasting clearly did not suppress circulating GH levels in mice, but resulted in an overall rise in mean GH levels, similar to that observed in other mammalian species. The fact that many of the fasting-induced changes in the GH axis were observed in the high-dose STZ-treated mice, but were not observed in the multiple, low-dose paradigm, suggests STZ-mediated modulation of GH axis function is dependent on the severity of the catabolic state and not hyperglycemia.
机译：在禁食和链脲佐菌素（STZ）诱导的糖尿病雄性大鼠中，下丘脑生长激素（GH）释放激素（GHRH）mRNA水平和搏动性GH释放降低。据信这些变化是由于抑制GHRH表达的下丘脑神经肽Y（NPY）的增加。为了直接测试是否需要NPY来调节对GH分泌很重要的下丘脑神经肽的代谢，在禁食（48 h）和经STZ处理的野生型（NPY（+ / +））中确定NPY，GHRH和生长抑素（SRIH）mRNA的水平）和NPY（-/-）小鼠的核糖核酸酶保护试验。另外，通过RT-PCR评估了GHRH（GHRH-R），ghrelin（GHS-R）和SRIH（sst2）的垂体受体mRNA水平。在进食条件下，NPY（+ / +）和NPY（-/-）的GH轴没有差异。在NPY（+ / +）小鼠中，禁食可导致23％的体重减轻和NPY mRNA的> 250％的增加，同时GHRH和SRIH mRNA均显着降低。这些变化与GHRH-R和GHS-R的垂体表达增加以及对sst2的抑制有关。在NPY（-/-）小鼠中，禁食也导致23％的体重减轻以及GHRH-R和sst2的可比变化，但未能改变GHRH，SRIH和GHS-R mRNA水平。空腹导致循环生长激素的总体增加，这在空腹NPY（-/-）小鼠中达到了重要意义。使用单次大剂量STZ注射（150 mg / kg）在NPY（+ / +）小鼠中诱导糖尿病，导致体重减轻（5％），NPY表达增加158％，这与垂体GHS-R和sst2表达的相互变化，与在禁食状态下观察到的相似，但未观察到下丘脑GHRH或SRIF表达的变化。使用多重低剂量STZ范例（连续5次每天注射40 mg / kg），在NPY（+ / +）和NPY（-/-）小鼠中诱导糖尿病并没有改变体重，下丘脑神经肽表达或垂体受体表达，但NPY（-/-）小鼠中sst2 mRNA水平受到抑制且GH水平确实升高。这些观察结果表明，NPY不是GH轴基础调节所必需的，而是空腹诱导的GHRH和SRIH表达抑制以及空腹诱导的垂体GHS-R mRNA增强所必需的。与大鼠相反，禁食显然不能抑制小鼠体内循环的GH水平，但会导致平均GH水平总体升高，这与其他哺乳动物物种中观察到的相似。在高剂量STZ处理的小鼠中观察到许多空腹诱导的GH轴变化，但在多重低剂量范例中未观察到这一事实，表明STZ介导的GH轴功能的调节是依赖的取决于分解代谢状态的严重程度，而非高血糖。

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