Regulation of alpha and rat luteinizing hormone-beta messenger ribonucleic acids during gonadotropin-releasing hormone agonist treatment in vivo in the male rat.
Agonist analogs of GnRH, after an initial period of stimulation, down-regulate gonadotropin secretion in both man and experimental animals. To study the pretranslational changes in LH subunits during GnRH agonist (GnRH-A) treatment in vivo, 55-day-old male Wistar rats were divided into two groups as follows: 1) sham operated, and 2) testosterone (T)-replaced castrated animals. T replacement was given by 20-mm T implants. Each group was subdivided into two subgroups to receive either saline or 1 microgram GnRH-A (D-Leu6,Des,Gly10-GnRH Net) by daily sc injection. Pituitaries were harvested after 1, 7, and 28 days of GnRH-A treatment for measurements of LH subunit mRNAs by dot hybridization assay. Serum LH concentrations were measured by a RIA. In intact animals, serum LH concentrations, measured 24 h after the GnRH-A injection, were higher in the GnRH-A group than in saline controls on day 1, but not on days 7 and 28. However, alpha and LH beta mRNA levels were higher in the GnRH-A-treated animals than in saline controls only on day 28, but not on days 1 and 7, however, in T-replaced castrated rats, in which testicular feedback to the pituitary was clamped by orchiectomy and replacement with a fixed dose of exogenous T, GnRH-A decreased serum LH and LH beta mRNA levels compared to those in saline controls. alpha mRNA levels were, however, not different between GnRH-A- and saline-treated animals at any time. We conclude that 1) an early increase in serum LH after 1 day of GnRH-A treatment probably reflects the release of preformed LH rather than increased synthesis; 2) in T-replaced castrated animals where the testicular feedback is clamped, GnRH-A-induced down-regulation of LH can be explained by a decrease in LH beta mRNA; and 3) differences in the LH subunit responses of intact and T-replaced castrated animals provide further evidence for testicular modulation of the LH response to GnRH-A.
D000818:Animals; D004343:Drug Implants; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000235:genetics*; D008297:Male; D009919:Orchiectomy; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013739:Testosterone / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D004343:Drug Implants; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D016729:Leuprolide