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. 1980 Aug;77(8):4459–4463. doi: 10.1073/pnas.77.8.4459

Direct inhibition of testicular function by gonadotropin-releasing hormone: mediation by specific gonadotropin-releasing hormone receptors in interstitial cells.

R N Clayton, M Katikineni, V Chan, M L Dufau, K J Catt
PMCID: PMC349863  PMID: 6254027

Abstract

Agonist analogs of gonadotropin-releasing hormone (GnRH) have been shown to exert antigonadal effects in male and female animals. In hypophysectomized male rats treated with follicle-stimulating hormone, administration of a potent GnRH agonist caused depletion of luteinizing hormone and prolactin receptors and marked suppression of serum testosterone levels. The possibility that such direct effects of GnRH agonists on testicular function could be expressed through specific receptors located in the interstitial cells of the testis was supported by the selective concentration of a 125I-labeled GnRH agonist by the testis in vivo. Specific receptors for the releasing hormone were demonstrated in testis particles and dispersed interstitial cells by direct binding analysis with the 125I-labeled GnRH agonist. The binding affinity (Ka = G X 10(9) M-1) and peptide specificity of the testicular GnRH binding sites were similar to those of anterior pituitary and ovarian GnRH receptors. The presence of GnRH receptors in the testis indicates that these sites mediate the direct inhibitory actions of GnRH agonists upon testicular endocrine function.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arimura A., Serafini P., Talbot S., Schally A. V. Reduction of testicular luteinizing hormone/human chorionic gonadotropin receptors by [D-Trp6]-luteinizing hormone releasing hormone in hypophysectomized rats. Biochem Biophys Res Commun. 1979 Oct 12;90(3):687–693. doi: 10.1016/0006-291x(79)91882-5. [DOI] [PubMed] [Google Scholar]
  2. Auclair C., Kelly P. A., Coy D. H., Schally A. V., Labrie F. Potent inhibitory activity of [D-Leu6, Des-Gly-NH2(10)]LHRH ethylamide on LH/hCG and PRL testicular receptor levels in the rat. Endocrinology. 1977 Dec;101(6):1890–1893. doi: 10.1210/endo-101-6-1890. [DOI] [PubMed] [Google Scholar]
  3. Auclair C., Kelly P. A., Labrie F., Coy D. H., Schally A. V. Inhibition of testicular luteinizing hormone receptor level by treatment with a potent luteinizing hormone-releasing hormone agonist of human chorionic gonadotropin. Biochem Biophys Res Commun. 1977 Jun 6;76(3):855–862. doi: 10.1016/0006-291x(77)91579-0. [DOI] [PubMed] [Google Scholar]
  4. Badger T. M., Beitins I. Z., Ostrea T., Crisafulli J. M., Little R., Saidel M. E. Luteinizing hormone-releasing hormone does not inhibit testosterone production in rat interstitial cells in vitro. Endocrinology. 1980 Apr;106(4):1149–1153. doi: 10.1210/endo-106-4-1149. [DOI] [PubMed] [Google Scholar]
  5. Bartke A., Steele R. E., Musto N., Caldwell B. V. Fluctuations in plasma testosterone levels in adult male rats and mice. Endocrinology. 1973 Apr;92(4):1223–1228. doi: 10.1210/endo-92-4-1223. [DOI] [PubMed] [Google Scholar]
  6. Catt K. J., Baukal A. J., Davies T. F., Dufau M. L. Luteinizing hormone-releasing hormone-induced regulation of gonadotropin and prolactin receptors in the rat testis. Endocrinology. 1979 Jan;104(1):17–25. doi: 10.1210/endo-104-1-17. [DOI] [PubMed] [Google Scholar]
  7. Clayton R. N., Harwood J. P., Catt K. J. Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production. Nature. 1979 Nov 1;282(5734):90–92. doi: 10.1038/282090a0. [DOI] [PubMed] [Google Scholar]
  8. Clayton R. N., Shakespear R. A., Duncan J. A., Marshall J. C., Munson P. J., Rodbard D. Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors. Endocrinology. 1979 Dec;105(6):1369–1376. doi: 10.1210/endo-105-6-1369. [DOI] [PubMed] [Google Scholar]
  9. Cusan L., Auclair C., Belanger A., Ferland L., Kelly P. A., Seguin C., Labrie F. Inhibitory effects of long term treatment with a luteinizing hormone-releasing hormone agonist on the pituitary-gonadal axis in male and female rats. Endocrinology. 1979 May;104(5):1369–1376. doi: 10.1210/endo-104-5-1369. [DOI] [PubMed] [Google Scholar]
  10. Davies T. F., Katikineni M., Chan V., Harwood J. P., Dufau M. L., Catt K. J. Lactogenic receptor regulation in hormone-stimulated steroidogenic cells. Nature. 1980 Feb 28;283(5750):863–865. doi: 10.1038/283863a0. [DOI] [PubMed] [Google Scholar]
  11. Dufau M. L., Catt K. J., Tsuruhara T., Ryan D. Radioimmunoassay of plasma testosterone. Clin Chim Acta. 1972 Mar;37:109–116. doi: 10.1016/0009-8981(72)90421-4. [DOI] [PubMed] [Google Scholar]
  12. Dufau M. L., Cigorraga S., Baukal A. J., Sorrell S., Bator J. M., Neubauer J. F., Catt K. J. Androgen biosynthesis in Leydig cells after testicular desensitization by luteinizing hormone-releasing hormone and human chorionic gonadotropin. Endocrinology. 1979 Dec;105(6):1314–1321. doi: 10.1210/endo-105-6-1314. [DOI] [PubMed] [Google Scholar]
  13. Dufau M. L., Mendelson C. R., Catt K. J. A highly sensitive in vitro bioassay for luteinizing hormone and chorionic gonadotropin: testosterone production by dispersed Leydig cells. J Clin Endocrinol Metab. 1974 Sep;39(3):610–613. doi: 10.1210/jcem-39-3-610. [DOI] [PubMed] [Google Scholar]
  14. Dufau M. L., Tsuruhara T., Horner K. A., Podesta E., Catt K. J. Intermediate role of adenosine 3':5'-cyclic monophosphate and protein kinase during gonadotropin-induced steroidogenesis in testicular interstitial cells. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3419–3423. doi: 10.1073/pnas.74.8.3419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Harwood J. P., Clayton R. N., Catt K. J. Ovarian gonadotropin-releasing hormone receptors. I. Properties and inhibition of luteal cell function. Endocrinology. 1980 Aug;107(2):407–413. doi: 10.1210/endo-107-2-407. [DOI] [PubMed] [Google Scholar]
  16. Harwood J. P., Clayton R. N., Chen T. T., Knox G., Catt K. J. Ovarian gonadotropin-releasing hormone receptors. II. Regulation and effects on ovarian development. Endocrinology. 1980 Aug;107(2):414–421. doi: 10.1210/endo-107-2-414. [DOI] [PubMed] [Google Scholar]
  17. Hsueh A. J., Erickson G. F. Extra-pituitary inhibition of testicular function by luteinising hormone releasing hormone. Nature. 1979 Sep 6;281(5726):66–67. doi: 10.1038/281066a0. [DOI] [PubMed] [Google Scholar]
  18. Hsueh A. J., Erickson G. F. Extrapituitary action of gonadotropin-releasing hormone: direct inhibition ovarian steroidogenesis. Science. 1979 May 25;204(4395):854–855. doi: 10.1126/science.375393. [DOI] [PubMed] [Google Scholar]
  19. Huhtaniemi I., Martikainen H. Rat testis LH/hCG recptors and testosterone production after treatment with GnRH. Mol Cell Endocrinol. 1978 Jul-Aug;11(2):199–204. doi: 10.1016/0303-7207(78)90007-2. [DOI] [PubMed] [Google Scholar]
  20. Ketelslegers J. M., Catt K. J. Follitropin receptors in rat testis. Characterization with enzymatically 125I-labeled human follitropin. Biochim Biophys Acta. 1978 Jul 3;541(3):360–371. doi: 10.1016/0304-4165(78)90195-2. [DOI] [PubMed] [Google Scholar]
  21. Mendelson C., Dufau M., Catt K. Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate and testosterone production in isolated Leydig cells. J Biol Chem. 1975 Nov 25;250(22):8818–8823. [PubMed] [Google Scholar]
  22. Pelletier G., Cusan L., Auclair C., Kelly P. A., Désy L., Labrie F. Inhibition of spermatogenesis in the rat by treatment with [D-Ala6, Des-Gly-NH210] LHRH ethylamide. Endocrinology. 1978 Aug;103(2):641–643. doi: 10.1210/endo-103-2-641. [DOI] [PubMed] [Google Scholar]
  23. Rippel R. H., Johnson E. S. Inhibition of HCG-induced ovarian and uterine weight augmentation in the immature rat by analogs of GnRH. Proc Soc Exp Biol Med. 1976 Jul;152(3):432–436. doi: 10.3181/00379727-152-39413. [DOI] [PubMed] [Google Scholar]
  24. Rivier C., Rivier J., Vale W. Chronic effects of [D-Trp6,Pro9-NEt]luteinizing hormone-releasing factor on reproductive processes in the male rat. Endocrinology. 1979 Nov;105(5):1191–1201. doi: 10.1210/endo-105-5-1191. [DOI] [PubMed] [Google Scholar]
  25. Rivier C., Vale W. Hormonal secretion in male rats chronically treated with [D-Trp6, Pro9-NEt]-LRF. Life Sci. 1979 Sep 17;25(12):1065–1074. doi: 10.1016/0024-3205(79)90592-7. [DOI] [PubMed] [Google Scholar]
  26. Ying S. Y., Guillemin R. DTrp6-Pro9-NEt)-luteinising hormone-releasing factor inhibits follicular development in hypophysectomised rats. Nature. 1979 Aug 16;280(5723):593–595. doi: 10.1038/280593a0. [DOI] [PubMed] [Google Scholar]

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