Further studies on the inactivation of thyrotrophin releasing hormone (TRH) by enzymes in the rat hypothalamus.
Thyrotrophin-releasing hormone (TRH) is known to be inactivated by enzymes present in the rat hypothalamus. To make a further study of the enzymes' action on the tripeptide, synthetic TRH was incubated with two hypothalamic subcellular fractions. By using a direct radioimmunoassay for TRH, the tripeptide was shown to be rapidly degraded by both supernatant and particulate fractions, with higher enzyme activity in the particulate fraction. Of several biologically-active peptides tested, only luteinizing hormone-releasing hormone was found to inhibit TRH inactivation; bacitracin, a polypeptide antibiotic, was also effective in inhibiting inactivation. Enzyme activity was highest in the middle hypothalamic area and lowest in the posterior hypothalamic area. Thin layer chromatography of the products of enzyme cleavage revealed the formation of only deamidated TRH in the supernatant fraction and the constitutent amino acids (pyroGlu, His, ProNH2) and histidylproline-diketopiperazine by the particular fraction, suggesting the presence of an amidase in the supernatant and two peptidases in the particulate fractions. These properties of the enzymes inactivating TRH may indicate that the enzymes could be of importance in regulating the endocrine and other functions attributed to this hypothalamic regulatory hormone.
D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013997:Time Factors
D005290:Ferric Compounds; D006728:Hormones; D001414:Bacitracin; D003035:Cobalt; D008345:Manganese; D013973:Thyrotropin-Releasing Hormone; D003300:Copper