title: The mechanism responsible for the supraphysiologic gonadotropin surge in females treated with gonadotropin-releasing hormone (GnRH) agonist and primed with GnRH antagonist.
abstract: OBJECTIVE
  To elucidate the physiologic mechanism responsible for the supraphysiologic gonadotropin release from the pituitary induced by gonadotropin-releasing hormone (GnRH) agonist in female rats primed with GnRH antagonist.
  
  
  METHODS
  Controlled experimental intervention.
  
  
  METHODS
  Government research facility.
  
  
  METHODS
  Forty 8-week-old Sprague-Dawley rats.
  
  
  METHODS
  Forty oophorectomized rats were randomized into four treatment groups of 10: group A, control vehicles; group B, GnRH agonist (leuprolide acetate; 1.7 microg/kg twice a day) on day 4; group C, GnRH antagonist (Nal-Lys; 3 mg/kg each day) days 1 to 4; or group D, GnRH antagonist (Nal-Lys; 3 mg/kg each day) days 1 to 4 plus GnRH agonist (1.7 microg/kg twice a day) on day 4.
  
  
  METHODS
  Immunohistochemical methods, Northern and in situ hybridization to quantitate pituitary follicle-stimulating hormone beta (FSH-beta), luteinizing hormone beta (LH-beta), and GnRH receptor (GnRH-R) messenger RNA (mRNA), and receptor protein levels in all treatment groups.
  
  
  RESULTS
  Treatment with GnRH antagonist was associated with increased storage of gonadotropin in the pituitary for FSH-beta and LH-beta, but mRNA levels were unchanged. The GnRH-R mRNA decreased after GnRH-agonist treatment but remained stable in the GnRH-antagonist treatment groups. Levels of GnRH-R were decreased after GnRH-antagonist treatment.
  
  
  CONCLUSIONS
  These data indicate that the in vivo mechanism responsible for the exaggerated release of gonadotropins in rats primed with GnRH antagonist and treated with GnRH agonist was an increase in releasable gonadotropin pools coupled with a reduction in GnRH-R, but receptor function was preserved.
authors.affiliation: Reproductive Biology and Medicine Branch, National Institutes of Health, Bethesda, Maryland 20814, USA.
authors.forename: Joelle E
authors.initials: JE
authors.lastname: Taylor
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Miller
authors.forename: Karen D
authors.initials: KD
authors.lastname: Gray
authors.forename: Richard T
authors.initials: RT
authors.lastname: Scott
authors.forename: William H
authors.initials: WH
authors.lastname: Catherino
authors.forename: James H
authors.initials: JH
authors.lastname: Segars
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D037201:Follicle Stimulating Hormone, beta Subunit / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006065:Gonadotropins, Pituitary / Q000235:genetics / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016729:Leuprolide / Q000494:pharmacology*; D037101:Luteinizing Hormone, beta Subunit / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010052:Ovariectomy; D010062:Ovulation Induction / Q000379:methods*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000187:drug effects / Q000378:metabolism
chemical_list: D005300:Fertility Agents, Female; D037201:Follicle Stimulating Hormone, beta Subunit; D006065:Gonadotropins, Pituitary; D006727:Hormone Antagonists; D037101:Luteinizing Hormone, beta Subunit; D009842:Oligopeptides; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; C057022:iturelix; D016729:Leuprolide