| Autor: |
Beak SA; Division of Endocrinology and Metabolic Medicine, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 ONN, United Kingdom., Heath MM, Small CJ, Morgan DG, Ghatei MA, Taylor AD, Buckingham JC, Bloom SR, Smith DM |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of clinical investigation [J Clin Invest] 1998 Mar 15; Vol. 101 (6), pp. 1334-41. |
| DOI: |
10.1172/JCI610 |
| Abstrakt: |
To examine the influence of the putative satiety factor (GLP-1) on the hypothalamo-pituitary-gonadal axis, we used GT1-7 cells as a model of neuronal luteinizing hormone- releasing hormone (LHRH) release. GLP-1 caused a concentration-dependent increase in LHRH release from GT1-7 cells. Specific, saturable GLP-1 binding sites were demonstrated on these cells. The binding of [125I]GLP-1 was time-dependent and consistent with a single binding site (Kd = 0.07+/-0.016 nM; binding capacity = 160+/-11 fmol/mg protein). The specific GLP-1 receptor agonists, exendin-3 and exendin-4, also showed high affinity (Ki = 0.3+/-0.05 and 0.32+/-0.06 nM, respectively) as did the antagonist exendin-(9-39) (Ki = 0.98+/-0.24 nM). At concentrations that increased LHRH release, GLP-1 (0.5-10 nM) also caused an increase in intracellular cAMP in GT1-7 cells (10 nM GLP-1: 7.66+/-0.4 vs. control: 0.23+/-0.02 nmol/mg protein; P < 0.001). Intracerebroventricular injection of GLP-1 at a single concentration (10 microg) produced a prompt increase in the plasma luteinizing hormone concentration in male rats (GLP-1: 1.09+/-0.11 vs. saline: 0.69+/-0.06 ng/ml; P < 0.005). GLP-1 levels in the hypothalami of 48-h-fasted male rats showed a decrease, indicating a possible association of the satiety factor with the low luteinizing hormone levels in animals with a negative energy balance. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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