title: Gonadal hormones and gonadotropin-releasing hormone (GnRH) alter messenger ribonucleic acid levels for GnRH receptors in sheep.
abstract: GnRH regulates the synthesis and secretion of pituitary gonadotropins. The number of receptors for GnRH (GnRH-rec) can vary from 500 to 15,000-20,000/gonadotrope in ovine pituitary cultures after treatment with physiologically relevant combinations of gonadal hormones. This large range suggests that regulation of GnRH-rec expression may be an important control point in GnRH action at the pituitary level. Reported here are the changes in GnRH-rec mRNA associated with pituitary treatments (48 h) of 17 beta-estradiol (E), progesterone (P), and an enriched preparation of porcine follicular inhibin (IN). Northern blot analysis was used to detect 3 species of GnRH-rec mRNA in primary ovine pituitary culture [5.5 kilobases (kb; 32%), 3.6 kb (51%), and 1.4 kb (17%)]; all were changed in parallel by E, P, and IN. GnRH-rec mRNAs were increased 190% over control levels after treatment with either E or IN, and 400% with E and IN combined; when E and IN were added along with P, the increase was only 50% (P caused an 87% inhibition of E plus IN induction). The addition of P in the absence of any other treatment reduced levels of GnRH-rec mRNA by 50%. Studies were also conducted with GnRH agonists (GnRH-A) due to their widespread clinical use for down-regulating reproductive function in men and women. The addition of GnRH-A to cultures was as effective as P in blocking E plus IN induction of GnRH-rec mRNA. In vivo studies in wethers showed that 7 days of chronic treatment with GnRH-A decreased all sizes of ovine GnRH-rec mRNA by 84-89%. These data indicate that E, P, and IN change GnRH-rec levels at least in part by changing levels of GnRH-rec mRNAs. They also show that GnRH-A can almost entirely block E plus IN induction of GnRH-rec mRNA in vitro and decrease levels of GnRH-rec mRNA in vivo in wethers.
authors.affiliation: Department of Biochemistry, North Carolina State University, Raleigh 27695-7622.
authors.forename: J C
authors.initials: JC
authors.lastname: Wu
authors.forename: S C
authors.initials: SC
authors.lastname: Sealfon
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D016729:Leuprolide / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011966:Receptors, LHRH / Q000187:drug effects* / Q000235:genetics*; D012756:Sheep; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide