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. 1980 Sep;77(9):5567–5571. doi: 10.1073/pnas.77.9.5567

Similar luteinizing hormone-releasing hormone binding sites in rat anterior pituitary and ovary.

J J Reeves, C Séguin, F A Lefebvre, P A Kelly, F Labrie
PMCID: PMC350103  PMID: 6254091

Abstract

To study the luteinizing hormone-releasing hormone (LH-RH; luliberin) receptors in the rat anterior pituitary gland and ovary, 125I-labeled [D-Ser(TBU)6des-Gly-NH2(10)]LH-RH ethylamide was used as a labeled ligand. The binding characteristics were assessed by Scatchard analysis of labeled ligand binding and by potency displacement with unlabeled peptides. Similar Kd values, ranging from 0.1 to 0.3 nM, were found for the labeled and unlabeled peptides in both tissues. A similar order of potency was observed between the finding affinity of 15 peptides in anterior pituitary and ovarian homogenates and their biological activity on luteinizing hormone release in rat anterior pituitary cells in culture. These data demonstrate that the LH-RH receptors present in the rat ovary have a specificity similar to that of the anterior pituitary LH-RH receptor controlling secretion of luteinizing hormone and follicle-stimulating hormone. Moreover, the binding affinities of the LH-RH agonists and antagonists can account, at least up to a large extent, for their relative biological potencies. Although there definitely are specific LH-RH receptors in the ovary which may play a role in the antifertility effects observed after administration of LH-RH agonists, the possible physiological significance of these ovarian receptors is still unknown and of great biological interest.

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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. Banik U. K., Givner M. L. Ovulation induction and antifertility effects of an LH-RH analogue (AY 25,205) in cyclic rats. J Reprod Fertil. 1975 Jul;44(1):87–94. doi: 10.1530/jrf.0.0440087. [DOI] [PubMed] [Google Scholar]
  3. Beattie C. W., Corbin A. Pre-and postcoital contraceptive activity of LH-RH in the rat. Biol Reprod. 1977 Apr;16(3):333–339. doi: 10.1095/biolreprod16.3.333. [DOI] [PubMed] [Google Scholar]
  4. Caron M. G., Beaulieu M., Raymond V., Gagné B., Drouin J., Lefkowitz R. J., Labrie F. Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release. J Biol Chem. 1978 Apr 10;253(7):2244–2253. [PubMed] [Google Scholar]
  5. Casper R. F., Yen S. S. Induction of luteolysis in the human with a long-acting analog of luteinizing hormone-releasing factor. Science. 1979 Jul 27;205(4404):408–410. doi: 10.1126/science.377491. [DOI] [PubMed] [Google Scholar]
  6. Cheng Y., Prusoff W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2. [DOI] [PubMed] [Google Scholar]
  7. Clayton R. N., Catt K. J. Receptor-binding affinity of gonadotropin-releasing hormone analogs: analysis by radioligand-receptor assay. Endocrinology. 1980 Apr;106(4):1154–1159. doi: 10.1210/endo-106-4-1154. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Clayton R. N., Shakespear R. A., Duncan J. A., Marshall J. C. Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies. Endocrinology. 1979 May;104(5):1484–1494. doi: 10.1210/endo-104-5-1484. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Conne B. S., Aubert M. L., Sizonenko P. C. Quantification of pituitary membrane receptor sites to LHRH: use of a superactive analog as tracer. Biochem Biophys Res Commun. 1979 Oct 29;90(4):1249–1256. doi: 10.1016/0006-291x(79)91171-9. [DOI] [PubMed] [Google Scholar]
  12. Coy D. H., Labrie F., Savary M., Coy E. J., Schally A. V. LH-releasing activity of potent LH-RH analogs in vitro. Biochem Biophys Res Commun. 1975 Nov 17;67(2):576–582. doi: 10.1016/0006-291x(75)90851-7. [DOI] [PubMed] [Google Scholar]
  13. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [DOI] [PubMed] [Google Scholar]
  14. Dias J. A., Reeves J. J. Disappearance of LHRH and D-Leu-des Gly NH2 LHRH ethylamide in ewes. J Anim Sci. 1978 Jun;46(6):1707–1711. doi: 10.2527/jas1978.4661707x. [DOI] [PubMed] [Google Scholar]
  15. Eskay R. L., Warberg J., Mical R. S., Porter J. C. Prostaglandin E2-induced release of LHRH into hypophysial portal blood(1). Endocrinology. 1975 Oct;97(4):816–824. doi: 10.1210/endo-97-4-816. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Hsueh A. J., Ling N. C. Effect on an antagonistic analog of gonadotropin releasing hormone upon ovarian granulosa cell function. Life Sci. 1979 Oct 1;25(14):1223–1229. doi: 10.1016/0024-3205(79)90464-8. [DOI] [PubMed] [Google Scholar]
  18. Johnson E. S., Seely J. H., White W. F., DeSombre E. R. Endocrine-dependent rat mammary tumor regression: use of a gonadotropin releasing hormone analog. Science. 1976 Oct 15;194(4262):329–330. doi: 10.1126/science.823643. [DOI] [PubMed] [Google Scholar]
  19. Kledzik G. S., Cusan L., Auclair C., Kelly P. A., Labrie F. Inhibition of ovarian luteinizing hormone (LH) and follicle-stimulating hormone receptor levels with an LH-releasing hormone agonist during the estrous cycle in the rat. Fertil Steril. 1978 Sep;30(3):348–353. doi: 10.1016/s0015-0282(16)43524-7. [DOI] [PubMed] [Google Scholar]
  20. Kledzik G. S., Cusan L., Auclair C., Kelly P. A., Labrie F. Inhibitory effect of a luteinizing hormone (LH)-releasing hormone agonist on rat ovarian LH and follicle-stimulating hormone receptor levels during pregnancy. Fertil Steril. 1978 May;29(5):560–564. doi: 10.1016/s0015-0282(16)43286-3. [DOI] [PubMed] [Google Scholar]
  21. Koch Y., Baram T., Hazum E., Fridkin M. Resistance to enzymic degradation of LH-RH analogues possessing increased biological activity. Biochem Biophys Res Commun. 1977 Jan 24;74(2):488–491. doi: 10.1016/0006-291x(77)90330-8. [DOI] [PubMed] [Google Scholar]
  22. Labrie F., Auclair C., Cusan L., Lemay A., Bélanger A., Kelly P. A., Ferland L., Azadian-Boulanger G., Raynaud J. P. Inhibitory effects of treatment with LHRH or its agonists on ovarian receptor levels and function. Adv Exp Med Biol. 1979;112:687–693. doi: 10.1007/978-1-4684-3474-3_75. [DOI] [PubMed] [Google Scholar]
  23. Labrie F., Savary M., Coy D. H., Coy E. J., Schally A. V. Inhibition of luteinizing hormone release by analogs of luteinizing hormone-releasing hormone (LHRH) in vitro. Endocrinology. 1976 Feb;98(2):289–294. doi: 10.1210/endo-98-2-289. [DOI] [PubMed] [Google Scholar]
  24. Lemay A., Labrie F., Azadian-Boulanger G., Raynaud J. P. Action lutéolytique de la LHRH chez la femme. C R Acad Sci Hebd Seances Acad Sci D. 1978 Feb 20;286(7):527–529. [PubMed] [Google Scholar]
  25. Lemay A., Labrie F., Belanger A., Raynaud J. P. Luteolytic effect of intranasal administration of [D-Ser(TBU)6,DES-Gly-NH2(10)]-luteinizing hormone-releasing hormone ethylamide in normal women. Fertil Steril. 1979 Dec;32(6):646–651. doi: 10.1016/s0015-0282(16)44412-2. [DOI] [PubMed] [Google Scholar]
  26. Lemay A., Labrie F., Ferland L., Raynaud J. P. Possible luteolytic effects of luteinizing hormone-releasing hormone in normal women. Fertil Steril. 1979 Jan;31(1):29–34. doi: 10.1016/s0015-0282(16)43755-6. [DOI] [PubMed] [Google Scholar]
  27. Macdonald G. J., Beattie C. W. Pregnancy failure in hypophysectomized rats following LH-RH administration. Life Sci. 1979 Mar 19;24(12):1103–1110. doi: 10.1016/0024-3205(79)90044-4. [DOI] [PubMed] [Google Scholar]
  28. Mayar M. Q., Tarnavsky G. K., Reeves J. J. Ovarian growth and uptake of iodinated D-leu, des Gly NH2 -LHRH ethylamide in HCG treated rats. Proc Soc Exp Biol Med. 1979 Jun;161(2):216–219. doi: 10.3181/00379727-161-40523. [DOI] [PubMed] [Google Scholar]
  29. Nett T. M., Akbar A. M., Niswender G. D. Serum levels of luteinizing hormone and gonadotropin-releasing hormone in cycling, castrated and anestrous ewes. Endocrinology. 1974 Mar;94(3):713–718. doi: 10.1210/endo-94-3-713. [DOI] [PubMed] [Google Scholar]
  30. Nillius S. J., Bergquist C., Wide L. Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue--a new approach to birth control? Contraception. 1978 Jun;17(6):537–545. [PubMed] [Google Scholar]
  31. Poirier G., De Lean A., Pelletier G., Lemay A., Labrie F. Purification of adenohypophyseal plasma membranes and properties of associated adenylate cyclase. J Biol Chem. 1974 Jan 10;249(1):316–322. [PubMed] [Google Scholar]
  32. Reeves J. J., Tarnavsky G. K., Becker S. R., Coy D., Schally A. V. Uptake of iodinated luteinizing hormone releasing hormone analogs in the pituitary. Endocrinology. 1977 Aug;101(2):540–547. doi: 10.1210/endo-101-2-540. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature. 1980 Mar 6;284(5751):17–22. doi: 10.1038/284017a0. [DOI] [PubMed] [Google Scholar]
  35. Sandow J., König W. Studies with fragments of a highly active analogue of luteinizing hormone releasing hormone. J Endocrinol. 1979 May;81(2):175–182. [PubMed] [Google Scholar]
  36. Wagner T. O., Adams T. E., Nett T. M. GNRH interaction with anterior pituitary. I. Determination of the affinity and number of receptors for GNRH in ovine anterior pituitary. Biol Reprod. 1979 Mar;20(2):140–149. doi: 10.1095/biolreprod20.2.140. [DOI] [PubMed] [Google Scholar]

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