Antagonism of pentobarbital-induced hormonal changes by TRH in rats.
In adult male rats, injection of TRH into a lateral ventricle of the brain 5 min prior to pentobarbital (PB) administration caused a significant dose-related inhibition of prolactin (PRL) release, in doses ranging from 500 to 5 ng. Among 8 TRH analogues devoid of thyrotropin-releasing activity, 6 were found to significantly suppress PB-induced PRL secretion at an intraventricular dose level of 10 microgram, and the 3 most effective in this respect were also able to counteract growth hormone (GH) release elicited by PB. The derivative [1,3'-DCM2]TRH was still potent enough to block PB-induced PRL secretion at an intraventricular dosage of 50 ng. The peptide ACTH 4--10 was ineffective, whereas another ACTH derivative H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) reduced PRL release. TRH did not affect the increase of plasma PRL induced by acute stress. alpha-Methyl-p-tyrosine (alpha-MT) failed to influence the inhibiting effect of TRH on GH secretion but significantly reduced that on PRL release. p-Chlorophenylalanine (PCPA) completely blocked the antagonistic effect of TRH on all PB-induced hormonal changes, suggesting that serotoninergic mechanisms may be involved in the extra-pituitary effect of TRH.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D010134:Fenclonine / Q000494:pharmacology; D013006:Growth Hormone / Q000097:blood*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D010424:Pentobarbital / Q000037:antagonists & inhibitors*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D013312:Stress, Physiological / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*
D008781:Methyltyrosines; D013973:Thyrotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D010424:Pentobarbital; D010134:Fenclonine