Regulation of the adenohypophyseal thyrotropin-releasing hormone-degrading ectoenzyme by estradiol.
TRH is inactivated by the TRH-degrading ectoenzyme, a TRH-specific metallopeptidase. At the pituitary level, this enzyme is stringently regulated by thyroid hormones. We describe here gender-related differences and the effect of estradiol (E2) on the expression of this enzyme in the anterior pituitary. Compared with male rats, only about one third of the enzymatic activities and the messenger RNA levels were found in the anterior pituitary of female rats, whereas the TRH receptor transcript levels were found inversely related. When male rats received a single injection of 0.5 microg E2/100 g BW, the enzymatic activity decreased to 65% of control values within 14 h, preceded by a decrease of the transcript levels to 25% of control within 6 h. Basal values were reached again 24-48 h after the injection. E2 had no effect on the expression of the enzyme in the brain. In vivo and with GH3 cells in vitro, E2 effectively counteracted the increase in enzymatic activity induced by T3, whereas neither testosterone nor progesterone, aldosterone, or dexamethasone showed any significant effects. Because the expression of the adenohypophyseal TRH-degrading ectoenzyme is tightly regulated by both T3 and E2 with adequate dynamics, we conclude that this peptidase serves integrative functions for the control of TRH-stimulated hormone secretion.
Schomburg
L
L
Max-Planck-Institut für experimentelle Endokrinologie, Hannover, Germany.
Bauer
K
K
D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics; D012727:Sex Characteristics; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology
D012333:RNA, Messenger; D018025:Receptors, Thyrotropin-Releasing Hormone; D014284:Triiodothyronine; D004958:Estradiol; D013973:Thyrotropin-Releasing Hormone; D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D011761:Pyrrolidonecarboxylic Acid