Action of gonadotropin-releasing hormone and its superactive analogues on the anterior pituitary: the mechanism of release and synthesis of gonadotropins.
The role of prostaglandins (PG), their active intermediates or the adenylcyclase-cyclic AMP system for gonadotropin release and/or synthesis was evaluated by administering gonadotropin-releasing hormone (Gn-RH) and its superactive analog to normal and aspirin-treated rats. Serum LH levels, anterior pituitary malondialdehyde (MDA) content and cyclic AMP (cAMP) levels were followed. The pituitaries stimulated with Gn-RH or its superactive analog yielded more MDA and cAMP than the controls. Stimulation of the pituitary with the releasing hormones, after aspirin treatment, yielded 40--70% less MDA and lower LH values than the nontreated animals. The cAMP levels were not significantly lowered by the aspirin treatment. These studies suggest that the activation of the PG biosynthesis and the adenyl-cyclase-cyclic AMP system are not sequential but 2 separate physiological events. The active PG intermediates may only be responsible for the release of LH. It is not clear whether the activation of cAMP initiates also the processes preparatory to the synthesis of LH in the endoplasmic reticulum. In vivo studies in rats showed that the analogs (I and II) were 30 times more potent and had a more prolonged action on the pituitary (3 h) than Gn-RH. Ultrastructural studies on the anterior pituitary after hypophyseal stalk portal vessel infusion of Gn-RH and the analog (I and II) provided ample morphological evidence for both Gn-RH and analog induced gonadotropin-release and synthesis. The prolonged action of the superactive analog (I and II) on the gonadotrophs was also indicated by ultrastructural studies.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006065:Gonadotropins, Pituitary / Q000096:biosynthesis*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats
D006065:Gonadotropins, Pituitary; D007987:Gonadotropin-Releasing Hormone; D008315:Malondialdehyde; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D001241:Aspirin