Mechanisms involved in the pituitary desensitization induced by gonadotropin-releasing hormone agonists.
OBJECTIVE
We investigated the mechanisms of desensitization induced by gonadotropin-releasing hormone agonist in the pituitary.


METHODS
Effects of gonadotropin-releasing hormone agonist on the pituitary were studied in vitro and in vivo in the rat. In the clinical study serum luteinizing hormone was measured by radioimmunoassay with a polyclonal luteinizing hormone antibody (luteinizing hormone-radioimmunoassay) and by immunoradiometric assay with monoclonal luteinizing hormone antibodies (luteinizing hormone-immunoradiometric assay) during gonadotropin-releasing hormone agonist treatment.


RESULTS
In the in vitro study bead-attached pituitary cells that were desensitized with a continuous infusion of 10(-7)mol/L gonadotropin-releasing hormone responded to 50 mmol/L K+. In the in vivo study gonadotropin-releasing hormone binding sites and rat luteinizing hormone beta-messenger ribonucleic acid in the pituitary decreased during gonadotropin-releasing hormone agonist treatment, but serum levels of rat luteinizing hormone did not decrease. In addition, a disparity between luteinizing hormone-radioimmunoassay and luteinizing hormone-immunoradiometric assay was demonstrated during gonadotropin-releasing hormone agonist treatment.


CONCLUSIONS
Pituitary desensitization in response to gonadotropin-releasing hormone agonist may not be wholly receptor mediated and a nonreceptor process may be involved.
Uemura
T
T
Department of Obstetrics and Gynecology, School of Medicine, Yokohama City University, Kanagawa Pref., Japan.
Yanagisawa
T
T
Shirasu
K
K
Matsuyama
A
A
Minaguchi
H
H
D000818:Animals; D002064:Buserelin / Q000494:pharmacology; D002478:Cells, Cultured; D004715:Endometriosis / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006801:Humans; D007247:Infertility, Female / Q000097:blood; D016729:Leuprolide / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D017274:Nafarelin / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011966:Receptors, LHRH / Q000378:metabolism
D012333:RNA, Messenger; D011966:Receptors, LHRH; D017274:Nafarelin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D016729:Leuprolide; D002064:Buserelin