Effects of central and peripheral type benzodiazepine ligands on thyrotropin and prolactin secretion.
The cold-stimulated thyrotropin (TSH) levels in the rat were decreased by clonazepam (a central type benzodiazepine agonist), diazepam (a mixed agonist), FG 7142 (an inverse central type agonist) and Ro 5-4864 (a peripheral type agonist), clonazepam being the most potent and Ro 5-4864 the least active. Clonazepam and diazepam also decreased while FG 7142 increased prolactin (PRL) levels. Ro 5-4864 did not have any significant action. Clonazepam (1 and 5 mg/kg) and diazepam (15 mg/kg but not 25 mg/kg) decreased even the TRH-induced PRL levels. Only Ro 5-4864 (25 mg/kg) decreased TRH-induced TSH secretion but not significantly. The actions of central type compounds were antagonized by flumazenil but not by PK 11195. The weak effects of Ro 5-4864 were not antagonized by either antagonists. While the peripheral type benzodiazepine agonist only weakly affected the secretion of anterior pituitary hormones, the central type inhibition of TSH appears to be mediated through the hypothalamic TRH and that of PRL rather through the anterior pituitary gland. The sedating (or agitating in case of FG 7142) effect of high doses of benzodiazepine ligands may contribute to the changes in TSH and PRL levels.
Järvinen
A
A
Department of Pharmacology, University of Helsinki, Finland.
Rägo
L
L
Männistö
P T
PT
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology*; D003080:Cold Temperature; D003975:Diazepam / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012636:Secretory Rate / Q000187:drug effects; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001570:Benzodiazepinones; D002243:Carbolines; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D005442:Flumazenil; D002998:Clonazepam; D013973:Thyrotropin-Releasing Hormone; C035874:FG 7142; D011388:Prolactin; D013972:Thyrotropin; D003975:Diazepam; C037850:PK 11195