Effects of gonadotropin-releasing hormone receptor blockade on rat testicular gonadotropin and lactogen receptors, steroidogenesis, and responses to human chorionic gonadotropin stimulation.
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.
Huhtaniemi
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Catt
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KJ
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
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