Thyrotropin-releasing hormone regulates the diurnal variation of pyroglutamyl aminopeptidase II activity in the male rat adenohypophysis.
OBJECTIVE
Thyrotropin-releasing hormone (TRH) is inactivated in the extracellular compartment by pyroglutamyl aminopeptidase II (PPII), a narrow specificity ectopeptidase present in the brain and in the lactotrophs of the adenohypophysis. TRH and various hypothalamic/paracrine agents regulate the activity of PPII on the surface of adenohypophyseal cells in primary culture. The activity of the hypothalamic-pituitary-thyroid axis presents circadian variations including an increase of serum thyrotropin levels in the early hours of the day. The purpose of this study was to determine whether adenohypophyseal PPII activity fluctuates during the daytime in the male rat and the role of TRH in these regulatory events in vivo.


RESULTS
Adenohypophyseal PPII specific activity and mRNA levels presented diurnal variations. A decrease in specific activity occurred with a minimum between 0930 and 1130 h, associated with increased serum thyrotropin levels. PPII mRNA levels were lowest at 0800 h. Intraperitoneal injection at 0800 or 1000 h of [3-Me-His(2)]-TRH, a potent agonist of the TRH receptor, reduced PPII specific activity at 30 min post-injection which was followed by a return to basal levels at 2 h. A second phase of decrease occurred between 4 and 8 h post-injection. Intravenous injection of a TRH-immune serum induced, at 2 h post-injection, an increase in adenohypophyseal PPII specific activity, which lasted up to 6 h.


CONCLUSIONS
Adenohypophyseal PPII activity and mRNA levels fluctuate during the day; TRH down-regulates PPII activity in vivo, contributing to some of these variations. These new findings, and previous data, suggest that adenohypophyseal PPII activity varies in distinct physiological events, in response to endocrine and hypothalamic/paracrine factors, potentially modulating responses to TRH.
Angel Vargas
Miguel
M
Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, A.P. 510-3, Cuernavaca, Morelos.
Uribe
Rosa María
RM
Cisneros
Miguel
M
Romero
Fidelia
F
González
Sergio
S
Joseph-Bravo
Patricia
P
Charli
Jean-Louis
JL
D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002940:Circadian Rhythm; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007106:Immune Sera / Q000008:administration & dosage; D007275:Injections, Intravenous; D008297:Male; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000819:agonists; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology*
D007106:Immune Sera; D012333:RNA, Messenger; D018025:Receptors, Thyrotropin-Releasing Hormone; C014109:thyrotropin-releasing hormone, 3-Me-; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D011761:Pyrrolidonecarboxylic Acid