Abribat T, Finkelstein J A, Gaudreau P
Neuroendocrinology Laboratory, Notre-Dame Hospital Research Center, University of Montreal, Canada.
Regul Pept. 1991 Oct 29;36(2):263-70. doi: 10.1016/0167-0115(91)90061-k.
The present study was designed to determine whether the diminution of growth hormone (GH) secretion that occurs in obese Zucker rats is related to alterations of GH-releasing factor (GRF) or somatostatin (SRIF) pituitary binding sites. Cold saturation studies were performed in pituitary homogenates of 4-month-old lean and obese rats, using [125I-Tyr10]hGRF(1-44)NH2 as radioligand and [127I-Tyr10]hGRF-(1-44)NH2 as competitor, and in pituitary membrane preparations, using [125I-Tyr0, D-Trp8]SRIF14 as radioligand and [127I-Tyr0, D-Trp8]SRIF14 as competitor. In lean rats, analysis of the curves by the Ligand program revealed the presence of two distinct classes of GRF binding sites, the first being of high affinity (0.74 +/- 0.11 nM) and low capacity (118 +/- 31 fmol/mg protein), the second being of lower affinity (880 +/- 240 nM) and higher capacity (140 +/- 35 pmol/mg protein), and of a single class of SRIF binding sites (affinity: 0.40 +/- 0.12 nM; capacity: 24 +/- 6 fmol/mg protein). In obese rats, no difference was observed in GRF binding parameters for both classes of sites, but the concentration of somatostatin binding sites was reduced by 67% when compared to their lean littermates. These findings suggest that the SRIF pituitary receptors are down-regulated in obese Zucker rats and indicate that no alteration of GRF pituitary binding sites contribute to the blunted GH secretion observed in this model of obesity.
本研究旨在确定肥胖Zucker大鼠中生长激素（GH）分泌减少是否与生长激素释放因子（GRF）或生长抑素（SRIF）垂体结合位点的改变有关。使用[125I-Tyr10]hGRF(1-44)NH2作为放射性配体，[127I-Tyr10]hGRF-(1-44)NH2作为竞争剂，对4个月大的瘦型和肥胖大鼠的垂体匀浆进行冷饱和研究；并使用[125I-Tyr0, D-Trp8]SRIF14作为放射性配体，[127I-Tyr0, D-Trp8]SRIF14作为竞争剂，对垂体膜制剂进行冷饱和研究。在瘦型大鼠中，通过Ligand程序分析曲线发现存在两类不同的GRF结合位点，第一类具有高亲和力（0.74±0.11 nM）和低容量（118±31 fmol/mg蛋白质），第二类具有较低亲和力（880±240 nM）和较高容量（140±35 pmol/mg蛋白质），以及一类单一的SRIF结合位点（亲和力：0.40±0.12 nM；容量：24±6 fmol/mg蛋白质）。在肥胖大鼠中，两类位点的GRF结合参数未观察到差异，但与瘦型同窝大鼠相比，生长抑素结合位点的浓度降低了67%。这些发现表明，肥胖Zucker大鼠的垂体SRIF受体下调，并且表明GRF垂体结合位点的改变对该肥胖模型中观察到的GH分泌减弱没有影响。
