title: LH down-regulates gonadotropin-releasing hormone (GnRH) receptor, but not GnRH, mRNA levels in the rat testis.
abstract: The demonstration of an inhibitory effect of gonadotropin-releasing hormone (GnRH) agonists upon steroidogenesis in hypophysectomized rats and the presence of mRNA coding for GnRH and GnRH receptors (GnRH-R) in rat gonads suggests that GnRH can act locally in the gonads. To assess this hypothesis, we investigated the effects of GnRH analogs, gonadotropins and testosterone on the levels of both GnRH and GnRH-R mRNA in the rat testis. Using dot blot hybridization, we measured the mRNA levels 2 to 120 h after the administration of the GnRH agonist, triptorelin. We observed an acute reduction of both GnRH and GnRH-R mRNAs 24 h after the injection (about 38% of control). However, the kinetics for testis GnRH-R mRNA were different from those previously found for pituitary GnRH-R mRNA under the same conditions. Initially, the concentrations of serum LH and FSH peaked, then declined, probably due to the desensitization of the gonadotrope cells. In contrast, the GnRH antagonist, antarelix, after 8 h induced a 2.5-fold increase in GnRH-R mRNA, but not in GnRH mRNA, while gonadotropins levels were reduced. Human recombinant FSH had no significant effect on either GnRH or GnRH-R mRNA levels. Inversely, GnRH-R mRNA levels markedly decreased by 21% of that of control 24 h after hCG injection. Finally, 24 h after testosterone injection, a significant increase in GnRH-R mRNA levels (2.3 fold vs control) was found, but a reduction in the concentration of serum LH, probably by negative feedback on the pituitary, was observed. In contrast, GnRH mRNA levels were not significantly altered following testosterone treatment. Since LH receptors, GnRH-R and testosterone synthesis are colocalized in Leydig cells, our data suggest that LH could inhibit the GnRH-R gene expression or decrease the GnRH-R mRNA stability in the testis. However, this does not exclude the possibility that GnRH analogs could also affect the GnRH-R mRNA levels via direct binding to testicular GnRH-R. In contrast, the regulation of GnRH mRNA levels appeared to be independent of gonadotropins. Taken together, our results suggest a regulation of GnRH and GnRH-R mRNA specific for the testis.
authors.affiliation: Endocrinologie Cellulaire et Moléculaire de la Reproduction, Université P&M Curie, CNRS ESA 7080, 75005 Paris, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Botté
authors.forename: Y
authors.initials: Y
authors.lastname: Lerrant
authors.forename: A
authors.initials: A
authors.lastname: Lozach
authors.forename: A
authors.initials: A
authors.lastname: Bérault
authors.forename: R
authors.initials: R
authors.lastname: Counis
authors.forename: M L
authors.initials: ML
authors.lastname: Kottler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D015151:Immunoblotting; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D017329:Triptorelin Pamoate / Q000494:pharmacology
chemical_list: D006063:Chorionic Gonadotropin; D009842:Oligopeptides; D012333:RNA, Messenger; D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; C084350:antarelix