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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1972 Sep;69(9):2677–2681. doi: 10.1073/pnas.69.9.2677

Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland In Vitro by Synthetic Luteinizing Hormone-Releasing Hormone

Pierre Borgeat *, Gerard Chavancy *, Andre Dupont *, Fernand Labrie *, Akita Arimura , Andrew V Schally
PMCID: PMC427015  PMID: 4341705

Abstract

A near-maximal dose (20 ng/ml) of synthetic luteinizing hormone(LH)-releasing hormone/follicle-stimulating hormone(FSH)-releasing hormone added to incubated anterior pituitary tissue of male rats leads to concomitant increases of intracellular concentrations of adenosine 3′:5′-monophosphate and of release of both LH and FSH. The stimulatory effect of LH-releasing hormone/FSH-releasing hormone is observed after a lag period of about 90 min and is progressive at later time intervals; a 3-fold stimulation of cAMP accumulation over control is seen after 210 min of incubation. Half-maximal stimulation of cAMP accumulation is observed between 0.1 and 1.0 ng/ml (0.1-1 nM) of LH-releasing hormone/FSH-releasing hormone. In the presence of 10 mM theophylline, the stimulatory effect of LH-releasing hormone/FSH-releasing hormone on cAMP accumulation is similar to that observed in the absence of the inhibitor of cyclic nucleotide phosphodiesterase, indicating that the releasing hormone exerts its effect by specific activation of adenylate cyclase in LH- and FSH-secreting cells rather than by inhibition of cyclic nucleotide phosphodiesterase. Since the release of growth hormone, thyrotropin, prolactin, and adrenocorticotropic hormone is not affected by LH-releasing hormone/FSH-releasing hormone, and since cAMP stimulates the release of all six adenohypophyseal hormones. the observed changes of cAMP concentrations indicate specific stimulation of adenylate cyclase activity in LH-and FSH-secreting cells of the adenohypophysis.

Keywords: adenylate cyclase, cyclic nucleotide phosphodiesterase, rat, follicle-stimulating hormone release, adenohypophysis

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Selected References

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  1. Amoss M., Burgus R., Blackwell R., Vale W., Fellows R., Guillemin R. Purification, amino acid composition and N-terminus of the hypothalamic luteinizing hormone releasing factor (LRF) of ovine origin. Biochem Biophys Res Commun. 1971 Jul 2;44(1):205–210. doi: 10.1016/s0006-291x(71)80179-1. [DOI] [PubMed] [Google Scholar]
  2. BERSON S. A., YALOW R. S., GLICK S. M., ROTH J. IMMUNOASSAY OF PROTEIN AND PEPTIDE HORMONES. Metabolism. 1964 Oct;13:SUPPL–SUPPL:1153. doi: 10.1016/s0026-0495(64)80031-7. [DOI] [PubMed] [Google Scholar]
  3. Baba Y., Matsuo H., Schally A. V. Structure of the porcine LH- and FSH-releasing hormone. II. Confirmation of the proposed structure by conventional sequential analyses. Biochem Biophys Res Commun. 1971 Jul 16;44(2):459–463. doi: 10.1016/0006-291x(71)90623-1. [DOI] [PubMed] [Google Scholar]
  4. Birge C. A., Peake G. T., Mariz I. K., Daughaday W. H. Radioimmunoassayable growth hormone in the rat pituitary gland: effects of age, sex and hormonal state. Endocrinology. 1967 Aug;81(2):195–204. doi: 10.1210/endo-81-2-195. [DOI] [PubMed] [Google Scholar]
  5. Burgus R., Butcher M., Ling N., Monahan M., Rivier J., Fellows R., Amoss M., Blackwell R., Vale W., Guillemin R. Structure moléculaire du facteur hypothalamique (LRF) d'origine ovine contrôlant la sécrétion de l'hormone gondadotrope hypophysaire de lutéinisation. C R Acad Sci Hebd Seances Acad Sci D. 1971 Nov 3;273(18):1611–1613. [PubMed] [Google Scholar]
  6. Burgus R., Guillemin R. Hypothalamic releasing factors. Annu Rev Biochem. 1970;39:499–526. doi: 10.1146/annurev.bi.39.070170.002435. [DOI] [PubMed] [Google Scholar]
  7. Cehovic G., Lewis U. J., Vande Laan W. P. Etude de l'action adénosine-3'-5'-monophosphate-cyclique sur la libération de l'hormone de croissance et de la prolactine in vitro. C R Acad Sci Hebd Seances Acad Sci D. 1970 Jun 22;270(25):3119–3122. [PubMed] [Google Scholar]
  8. Cehovic G., Marcus I., Gabbai A., Posternak T. Etude de l'action de certains nouveaux analogues de l'AMP cyclique sur la libération de l'hormone de croissance et de la prolactine in vitro. C R Acad Sci Hebd Seances Acad Sci D. 1970 Oct 19;271(16):1399–1401. [PubMed] [Google Scholar]
  9. DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
  10. Faiman C., Ryan R. J. Radioimmunoassay for human follicle stimulating hormone. J Clin Endocrinol Metab. 1967 Mar;27(3):444–447. doi: 10.1210/jcem-27-3-444. [DOI] [PubMed] [Google Scholar]
  11. Fleischer N., Donald R. A., Butcher R. W. Involvement of adenosine 3',5'-monophosphate in release of ACTH. Am J Physiol. 1969 Nov;217(5):1287–1291. doi: 10.1152/ajplegacy.1969.217.5.1287. [DOI] [PubMed] [Google Scholar]
  12. GADDUM J. H. Bioassays and mathematics. Pharmacol Rev. 1953 Mar;5(1):87–134. [PubMed] [Google Scholar]
  13. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Geiger R., König W., Wissmann H., Geisen K., Enzmann F. Synthesis and characterisation of a decapeptide having LH-RH-FSH-RH activity. Biochem Biophys Res Commun. 1971 Nov 5;45(3):767–773. doi: 10.1016/0006-291x(71)90483-9. [DOI] [PubMed] [Google Scholar]
  15. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guillemin R. Physiology and chemistry of the hypothalamic releasing factors for gonadotropins: a new approach to fertility control. Contraception. 1972 Jan;5(1):1–19. doi: 10.1016/0010-7824(72)90076-5. [DOI] [PubMed] [Google Scholar]
  17. Jutisz M., Paloma de la Llosa M. Requirement of Ca++ and Mg++ ions for the in vitro release of follicle-stimulating hormone from rat pituitary glands and in its subsequent biosynthesis. Endocrinology. 1970 Apr;86(4):761–768. doi: 10.1210/endo-86-4-761. [DOI] [PubMed] [Google Scholar]
  18. Kastin A. J., Schally A. V., Gual C., Midgley A. R., Jr, Bowers C. Y., Gomez-Perez F. Administration of LH-releasing hormone to selected subjects. Am J Obstet Gynecol. 1970 Sep 15;108(2):177–182. doi: 10.1016/0002-9378(70)90293-0. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Labrie F., Barden N., Poirier G., De Lean A. Binding of thyrotropin-releasing hormone to plasma membranes of bovine anterior pituitary gland (hormone receptor-adenylate cyclase-equilibrium constant-( 3 H)thyrotropin). Proc Natl Acad Sci U S A. 1972 Jan;69(1):283–287. doi: 10.1073/pnas.69.1.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Labrie F., Béraud G., Gauthier M., Lemay A. Actinomycin-insensitive stimulation of protein synthesis in rat anterior pituitary in vitro by dibutyryl adenosine 3',5'-monophosphate. J Biol Chem. 1971 Mar 25;246(6):1902–1908. [PubMed] [Google Scholar]
  22. Labrie F., Lemaire S., Courte C. Adenosine 3',5'-monophosphate-dependent protein kinase from bovine anterior pituitary gland. I. Properties. J Biol Chem. 1971 Dec 10;246(23):7293–7302. [PubMed] [Google Scholar]
  23. Labrie F., Lemaire S., Poirier G., Pelletier G., Boucher R. Adenohypophyseal secretory granules. I. Their phosphorylation and association with protein kinase. J Biol Chem. 1971 Dec 10;246(23):7311–7317. [PubMed] [Google Scholar]
  24. Lemaire S., Pelletier G., Labrie F. Adenosine 3',5'-monophosphate-dependent protein kinase from bovine anterior pituitary gland. II. Subcellular distribution. J Biol Chem. 1971 Dec 10;246(23):7303–7310. [PubMed] [Google Scholar]
  25. Lemay A., Labrie F. Calcium-dependent stimulation of prolactin release in rat anterior pituitary in vitro by n(6)-monobutyryl adenosine 3',5'-monophosphate. FEBS Lett. 1972 Jan 15;20(1):7–10. doi: 10.1016/0014-5793(72)80003-6. [DOI] [PubMed] [Google Scholar]
  26. Matsuo H., Arimura A., Nair R. M., Schally A. V. Synthesis of the porcine LH- and FSH-releasing hormone by the solid-phase method. Biochem Biophys Res Commun. 1971 Nov 5;45(3):822–827. doi: 10.1016/0006-291x(71)90491-8. [DOI] [PubMed] [Google Scholar]
  27. Matsuo H., Baba Y., Nair R. M., Arimura A., Schally A. V. Structure of the porcine LH- and FSH-releasing hormone. I. The proposed amino acid sequence. Biochem Biophys Res Commun. 1971 Jun 18;43(6):1334–1339. doi: 10.1016/s0006-291x(71)80019-0. [DOI] [PubMed] [Google Scholar]
  28. McCann S. M., Porter J. C. Hypothalamic pituitary stimulating and inhibiting hormones. Physiol Rev. 1969 Apr;49(2):240–284. doi: 10.1152/physrev.1969.49.2.240. [DOI] [PubMed] [Google Scholar]
  29. McKENZIE J. M. The bioassay of thyrotropin in serum. Endocrinology. 1958 Sep;63(3):372–382. doi: 10.1210/endo-63-3-372. [DOI] [PubMed] [Google Scholar]
  30. Midgley A. R., Jr Radioimmunoassay: a method for human chorionic gonadotropin and human luteinizing hormone. Endocrinology. 1966 Jul;79(1):10–18. doi: 10.1210/endo-79-1-10. [DOI] [PubMed] [Google Scholar]
  31. Midgley A. R. Radioimmunoassay for human follicle-stimulating hormone. J Clin Endocrinol Metab. 1967 Feb;27(2):295–299. doi: 10.1210/jcem-27-2-295. [DOI] [PubMed] [Google Scholar]
  32. Milhaud G., Rivaille P., Garnier P., Chaussain J. L., Binet E., Job J. C. Synthèse de la LH-RH et effet sélectif sur la libération de l'hormone lutéotrophique chez l'homme adulte. C R Acad Sci Hebd Seances Acad Sci D. 1971 Nov 15;273(20):1858–1861. [PubMed] [Google Scholar]
  33. Monahan M., Rivier J., Burgus R., Amoss M., Blackwell R., Vale W., Guillemin R. Synthèse totale par phase solide d'un décapeptide qui stimule la sécrétion des gonadotropines hypophysaires LH et FS. C R Acad Sci Hebd Seances Acad Sci D. 1971 Jul 26;273(4):508–510. [PubMed] [Google Scholar]
  34. Odell W. D., Rayford P. L., Ross G. T. Simplified, partially automated method for radioimmunoassay of human thyroid-stimulating, growth, luteinizing, and follicle stimulating hormones. J Lab Clin Med. 1967 Dec;70(6):973–980. [PubMed] [Google Scholar]
  35. Peake G. T., Steiner A. L., Daughaday W. H. Guanosine 3'5' cyclic monophosphate is a potent pituitary growth hormone secretogogue. Endocrinology. 1972 Jan;90(1):212–216. doi: 10.1210/endo-90-1-212. [DOI] [PubMed] [Google Scholar]
  36. Poirier G., Labrie F., Barden N., Lemaire S. Thyrotropin-releasing hormone receptor: Its partial purification from bovine anterior pituitary gland and its close association with adenyl cyclase. FEBS Lett. 1972 Feb 15;20(3):283–286. doi: 10.1016/0014-5793(72)80087-5. [DOI] [PubMed] [Google Scholar]
  37. Posternak T., Marcus I., Cehovic G. Préparation de nouveaux dérivés de l'AMPc (substitués en position C-8 et C-2) et étude de leur action sur la libération de l'hormone de croissance. C R Acad Sci Hebd Seances Acad Sci D. 1971 Jan 25;272(4):622–625. [PubMed] [Google Scholar]
  38. Ratner A. Stimulation of luteinizing hormone release in vitro by dibutyryl-cyclic-AMP and theophylline. Life Sci I. 1970 Nov 1;9(21):1221–1226. doi: 10.1016/0024-3205(70)90155-4. [DOI] [PubMed] [Google Scholar]
  39. SAKIZ E., GUILLEMIN R. ON A METHOD FOR CALCULATION AND ANALYSIS OF RESULTS IN THE MCKENZIE ASSAY FOR THYROTROPIN (TSH). Proc Soc Exp Biol Med. 1964 Apr;115:856–860. doi: 10.3181/00379727-115-29057. [DOI] [PubMed] [Google Scholar]
  40. Schally A. V., Arimura A., Baba Y., Nair R. M., Matsuo H., Redding T. W., Debeljuk L. Isolation and properties of the FSH and LH-releasing hormone. Biochem Biophys Res Commun. 1971 Apr 16;43(2):393–399. doi: 10.1016/0006-291x(71)90766-2. [DOI] [PubMed] [Google Scholar]
  41. Schally A. V., Arimura A., Bowers C. Y., Kastin A. J., Sawano S., Reeding T. W. Hypothalamic neurohormones regulating anterior pituitary function. Recent Prog Horm Res. 1968;24:497–588. doi: 10.1016/b978-1-4831-9827-9.50016-2. [DOI] [PubMed] [Google Scholar]
  42. Schally A. V., Arimura A., Kastin A. J., Matsuo H., Baba Y., Redding T. W., Nair R. M., Debeljuk L., White W. F. Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science. 1971 Sep 10;173(4001):1036–1038. doi: 10.1126/science.173.4001.1036. [DOI] [PubMed] [Google Scholar]
  43. Schally A. V., Baba Y., Redding T. W., Matsuo H., Arimura A. Further studies on the enzymatic and chemical inactivation of hypothalamic FSH-RH. Neuroendocrinology. 1971;8(6):347–358. doi: 10.1159/000122022. [DOI] [PubMed] [Google Scholar]
  44. Schally A. V., Kastin A. J., Arimura A. Hypothalamic follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-regulating hormone: structure, physiology, and clinical studies. Fertil Steril. 1971 Nov;22(11):703–721. [PubMed] [Google Scholar]
  45. Schally A. V., Nair R. M., Redding T. W., Arimura A. Isolation of the luteinizing hormone and follicle-stimulating hormone-releasing hormone from porcine hypothalami. J Biol Chem. 1971 Dec 10;246(23):7230–7236. [PubMed] [Google Scholar]
  46. Swallow R. L., Sayers G. A technic for the preparation of isolated rat adrenal cells. Proc Soc Exp Biol Med. 1969 May;131(1):1–4. doi: 10.3181/00379727-131-33789. [DOI] [PubMed] [Google Scholar]
  47. White W. F., Schally A. V., Baba Y., Arimura A., Redding T. W. Evidence for peptide nature of LH and FSH-releasing hormones. Biochem Biophys Res Commun. 1971 Jan 8;42(1):50–56. doi: 10.1016/0006-291x(71)90360-3. [DOI] [PubMed] [Google Scholar]
  48. Wilber J. F., Peake G. T., Utiger R. D. Thyrotropin release in vitro: stimulation by cyclic 3',5'-Adenosine monophosphate. Endocrinology. 1969 Apr;84(4):758–760. doi: 10.1210/endo-84-4-758. [DOI] [PubMed] [Google Scholar]
  49. Zor U., Kaneko T., Schneider H. P., McCann S. M., Field J. B. Further studies of stimulation of anterior pituitary cyclic adenosine 3',5'-monophosphate formation by hypothalamic extract and prostaglandins. J Biol Chem. 1970 Jun 10;245(11):2883–2888. [PubMed] [Google Scholar]
  50. Zor U., Kaneko T., Schneider H. P., McCann S. M., Lowe I. P., Bloom G., Borland B., Field J. B. Stimulation of anterior pituitary adenyl cyclase activity and adenosine 3':5'-cyclic phosphate by hypothalamic extract and prostaglandin E1. Proc Natl Acad Sci U S A. 1969 Jul;63(3):918–925. doi: 10.1073/pnas.63.3.918. [DOI] [PMC free article] [PubMed] [Google Scholar]

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