Glucagon-like peptide-1 stimulates luteinizing hormone-releasing hormone secretion in a rodent hypothalamic neuronal cell line.
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.
Beak
S A
SA
Division of Endocrinology and Metabolic Medicine, Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 ONN, United Kingdom.
Heath
M M
MM
Small
C J
CJ
Morgan
D G
DG
Ghatei
M A
MA
Taylor
A D
AD
Buckingham
J C
JC
Bloom
S R
SR
Smith
D M
DM
D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000077270:Exenatide; D005508:Food Deprivation; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014688:Venoms
D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D014688:Venoms; C066448:exendin 3; D007987:Gonadotropin-Releasing Hormone; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D007986:Luteinizing Hormone; D005934:Glucagon; D000077270:Exenatide; D000242:Cyclic AMP; D002118:Calcium