title: Effects of gonadotropin-releasing hormone receptor blockade on rat testicular gonadotropin and lactogen receptors, steroidogenesis, and responses to human chorionic gonadotropin stimulation.
abstract: Testicular endocrine regulation was studied in adult male rats after treatment with a potent GnRH antagonist analog [N-Ac-D-p-Cl-Phe1,2, D-Trp3, D-Lys6, D-Ala10-GnRH (Ant.)] given in doses of 1 mg/kg at 0, 12, and 24 h. One group of animals also received an injection of human CG (hCG) (600 IU/kg) at 12 h, and all animals were killed at 36 h for hormone and receptor (R) measurements. Treatment with Ant. blocked greater than 95% of the pituitary and testicular GnRH-R, and decreased serum LH concentration by greater than 90%. Testicular lactogen-R content was decreased by 60% (P less than 0.01), but there was no change in LH-R and FSH-R concentrations. Ant. decreased serum and testicular testosterone levels by 90%, and testicular capacity to produce testosterone in vitro by 50% (P less than 0.01). No decrease was observed in production rates of cAMP and progesterone. hCG alone abolished testicular LH-R, decreased lactogen-R by 55% (P less than 0.01), and GnRH-R by 65% (P less than 0.01). Desensitization of cAMP and testosterone production, and an increase in progesterone-testosterone ratio, were seen after hCG. hCG + Ant. treatment resulted in R, cAMP, and steroid responses that were indistinguishable from those seen after hCG alone. These findings indicate that: 1) Ant.-induced hypogonadotropism decreases testicular lactogen-R concentration and testosterone production; 2) testicular GnRH-R and lactogen-R are subject to heterologous down-regulation by hCG; and 3) inhibition of the putative GnRH-mediated regulation of testis by Ant. blockade of the GnRH-R does not change testicular response to hCG-treatment in vivo. Hence, the present observations still leave the physiological role of testicular GnRH-R open.
authors.forename: I T
authors.initials: IT
authors.lastname: Huhtaniemi
authors.forename: K J
authors.initials: KJ
authors.lastname: Catt
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011962:Receptors, FSH; D011974:Receptors, LH; D011966:Receptors, LHRH; D018000:Receptors, Peptide; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis
chemical_list: D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011962:Receptors, FSH; D011974:Receptors, LH; D011966:Receptors, LHRH; D018000:Receptors, Peptide; C028202:placental lactogen receptor; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D011374:Progesterone; C043124:N-Ac-(4-Cl-Phe)(1)-(4-Cl-Phe)(2)-Trp(3)-Lys(6)-AlaNH2(10)-LHRH; D007986:Luteinizing Hormone; D000242:Cyclic AMP