Effects of central and peripheral type benzodiazepine ligands on growth hormone and gonadotropin secretion in male rats.
The action of central and peripheral type benzodiazepine ligands on growth hormone, luteinizing hormone and follicle stimulating hormone levels in serum were studied in male rats. Graded doses of Ro 5-4864, that binds to the peripheral type benzodiazepine receptors, clonazepam, a fairly pure central type agonist and diazepam, a mixed-type agonist, were given intraperitoneally. Also a benzodiazepine partial inverse agonist, FG 7142, was investigated. Clonazepam increased growth hormone levels at 0.2 mg/kg while higher doses were not active. Diazepam (5-25 mg/kg) was not effective. FG 7142 (15 mg/kg) and Ro 5-4864 (25 mg/kg) decreased growth hormone levels. Flumazenil, a central-type antagonist, reversed at least partially the effects of clonazepam and FG 7142, suggesting an effect through GABA-benzodiazepine complex. Elevation of growth hormone could be associated with anxiolysis and decrease of growth hormone with enhanced anxiety. Clonazepam (0.2-5 mg/kg) and diazepam (5-25 mg/kg) increased luteinizing hormone concentrations, but only the effects of 1 mg/kg of clonazepam and 5 mg/kg of diazepam reached statistical significance. Even FG 7142 caused a modest increase of luteinizing hormone at 5 mg/kg, but Ro 5-4864 rather decreased luteinizing hormone, although not significantly. Flumazenil (25 mg/kg) antagonized partially the effects of diazepam and clonazepam. Effects of Ro 5-4864 and FG 7142 were not modified by flumazenil or PK 11195, a peripheral-type mixed antagonist/agonist. Luteinizing hormone stimulation by benzodiazepine ligands may be a pituitary action while inhibition could be caused by the activation of the central GABAergic system. Serum follicle stimulating hormone levels were not significantly altered by central or peripheral type benzodiazepine agonists or antagonists.
Männistö
P T
PT
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Laakso
M L
ML
Järvinen
A
A
Rägo
L
L
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood*; D013006:Growth Hormone / Q000097:blood*; D007274:Injections, Intraperitoneal; D008024:Ligands; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism
D008024:Ligands; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone