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. 1970 Nov;67(3):1172–1179. doi: 10.1073/pnas.67.3.1172

Release of Pituitary Growth Hormone by Prostaglandins and Dibutyryl Adenosine Cyclic 3′:5′-Monophosphate in the Absence of Protein Synthesis

Robert M MacLeod 1, Joyee E Lehmeyer 1
PMCID: PMC283333  PMID: 4320973

Abstract

Effects of prostaglandins on the incorporation of [4,5-3H]leucine into growth hormone and its subsequent release into the incubation medium were studied. Incubation of rat anterior pituitary glands with 10-6 M prostaglandin PGE1 in tissue culture medium 199 for 7 hr caused a 40-300% increase in the release of labeled growth hormone into the incubation medium. PGE1 at 10-8 M increased growth hormone synthesis but not release. At 10-6 M, PGE2 had effects similar to PGE1; PGA1 increased growth hormone synthesis but not release. PGF2α was without effect on either synthesis or release of growth hormone.

Prolactin synthesis and release were not affected by prostaglandins. All of the prostaglandins, at 10-4 M, increased adenyl cyclase activity in the pituitary gland but phosphodiesterase activity was unaltered. Dibutyryl cyclic AMP, with or without caffeine, caused an up to 300% increase in labeled growth hormone release. No consistent effect of prolactin was observed. If potassium concentration was increased 10-fold, a 215% increase in growth hormone release was observed. A combination of hypertonic potassium and 10-6 M PGE1 increased growth hormone release 325%, suggesting that potassium and prostaglandins act by independent mechanisms. Addition of theophylline to pituitary gland, incubated in vitro, increased both the synthesis and release of growth hormone. Although fluoride greatly stimulated growth hormone release, it completely inhibited the incorporation of leucine into the hormone. Similarly, puromycin inhibited synthesis of growth hormone but did not block release induced by prostaglandin, dibutyryl cyclic AMP, theophylline, or fluoride. Prostaglandins increase pituitary adenyl cyclase activity and, presumably via cyclic AMP, increase growth hormone release, independently of protein synthesis.

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Selected References

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  1. Ahn C. S., Rosenberg I. N. Proteolysis in thyroid slices: Effects of TSH, dibutyryl cyclic 3', 5'-AMP and prostaglandin E. Endocrinology. 1970 Apr;86(4):870–873. doi: 10.1210/endo-86-4-870. [DOI] [PubMed] [Google Scholar]
  2. BUTCHER R. W., SUTHERLAND E. W. Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J Biol Chem. 1962 Apr;237:1244–1250. [PubMed] [Google Scholar]
  3. Bergström S. Prostaglandins: members of a new hormonal system. These physiologically very potent compounds of ubiquitous occurrence are formed from essential fatty acids. Science. 1967 Jul 28;157(3787):382–391. doi: 10.1126/science.157.3787.382. [DOI] [PubMed] [Google Scholar]
  4. Birnbaumer L., Pohl S. L., Rodbell M. Adenyl cyclase in fat cells. 1. Properties and the effects of adrenocorticotropin and fluoride. J Biol Chem. 1969 Jul 10;244(13):3468–3476. [PubMed] [Google Scholar]
  5. Butcher R. W., Baird C. E. Effects of prostaglandins on adenosine 3',5'-monophosphate levels in fat and other tissues. J Biol Chem. 1968 Apr 25;243(8):1713–1717. [PubMed] [Google Scholar]
  6. Butcher R. W., Sutherland E. W. The effects of the catecholamines, adrenergic blocking agents, prostaglandin E1, and insulin on cyclie AMP levels in the rat epididymal fat pad in vitro. Ann N Y Acad Sci. 1967 Feb 10;139(3):849–859. doi: 10.1111/j.1749-6632.1967.tb41255.x. [DOI] [PubMed] [Google Scholar]
  7. Bär H. P., Hechter O. Adenyl cyclase and hormone action. I. Effects of adrenocorticotropic hormone, glucagon, and epinephrine on the plasma membrane of rat fat cells. Proc Natl Acad Sci U S A. 1969 Jun;63(2):350–356. doi: 10.1073/pnas.63.2.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Flack J. D., Jessup R., Ramwell P. W. Prostaglandin stimulation of rat corticosteroidogenesis. Science. 1969 Feb 14;163(3868):691–692. doi: 10.1126/science.163.3868.691. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Grahame-Smith D. G., Butcher R. W., Ney R. L., Sutherland E. W. Adenosine 3',5'-monophosphate as the intracellular mediator of the action of adrenocorticotropic hormone on the adrenal cortex. J Biol Chem. 1967 Dec 10;242(23):5535–5541. [PubMed] [Google Scholar]
  11. HAYNES R. C., Jr, SUTHERLAND E. W., RALL T. W. The role of cyclic adenylic acid in hormone action. Recent Prog Horm Res. 1960;16:121–138. [PubMed] [Google Scholar]
  12. JONES A. E., FISHER J. N., LEWIS U. J., VANDERLAAN W. P. ELECTROPHORETIC COMPARISON OF PITUITARY GLANDS FROM MALE AND FEMALE RATS. Endocrinology. 1965 Apr;76:578–583. doi: 10.1210/endo-76-4-578. [DOI] [PubMed] [Google Scholar]
  13. KLAINER L. M., CHI Y. M., FREIDBERG S. L., RALL T. W., SUTHERLAND E. W. Adenyl cyclase. IV. The effects of neurohormones on the formation of adenosine 3',5'-phosphate by preparations from brain and other tissues. J Biol Chem. 1962 Apr;237:1239–1243. [PubMed] [Google Scholar]
  14. KLAINER L. M., CHI Y. M., FREIDBERG S. L., RALL T. W., SUTHERLAND E. W. Adenyl cyclase. IV. The effects of neurohormones on the formation of adenosine 3',5'-phosphate by preparations from brain and other tissues. J Biol Chem. 1962 Apr;237:1239–1243. [PubMed] [Google Scholar]
  15. Kaneko T., Zor U., Field J. B. Thyroid-stimulating hormone and prostaglandin E1 stimulation of cyclic 3',5'-adenosine monophosphate in thyroid slices. Science. 1969 Mar 7;163(3871):1062–1063. doi: 10.1126/science.163.3871.1062. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. MURAD F., CHI Y. M., RALL T. W., SUTHERLAND E. W. Adenyl cyclase. III. The effect of catecholamines and choline esters on the formation of adenosine 3',5'-phosphate by preparations from cardiac muscle and liver. J Biol Chem. 1962 Apr;237:1233–1238. [PubMed] [Google Scholar]
  18. MacLeod R. M., Abad A. On the control of prolactin and growth hormone synthesis in rat pituitary glands. Endocrinology. 1968 Oct;83(4):799–806. doi: 10.1210/endo-83-4-799. [DOI] [PubMed] [Google Scholar]
  19. MacLeod R. M., Fontham E. H. Influence of ionic environment on the in vitro synthesis and release of pituitary hormones. Endocrinology. 1970 Apr;86(4):863–869. doi: 10.1210/endo-86-4-863. [DOI] [PubMed] [Google Scholar]
  20. MacLeod R. M. Influence of norepinephrine and catecholamine-depleting agents on the synthesis and release of prolactin and growth hormone. Endocrinology. 1969 Nov;85(5):916–923. doi: 10.1210/endo-85-5-916. [DOI] [PubMed] [Google Scholar]
  21. MacLeod R. M., Smith M. C., DeWitt G. W. Hormonal properties of transplanted pituitary tumors and their relation to the pituitary gland. Endocrinology. 1966 Dec;79(6):1149–1156. doi: 10.1210/endo-79-6-1149. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Peng T. C., Six K. M., Munson P. L. Effects of prostaglandin E-1 on the hypothalamo-hyophyseal-adrenocortical axis in rats. Endocrinology. 1970 Feb;86(2):202–206. doi: 10.1210/endo-86-2-202. [DOI] [PubMed] [Google Scholar]
  24. Samli M. H., Geschwind I. I. Some effects of energy-transfer inhibitors and of Ca++-free or K+-enhanced media on the release of luteinizing hormone (LH) from the rat pituitary gland in vitro. Endocrinology. 1968 Feb;82(2):225–231. doi: 10.1210/endo-82-2-225. [DOI] [PubMed] [Google Scholar]
  25. Schally A. V., Muller E. E., Arimura A., Saito T., Sawano S., Bowers C. Y., Steelman S. L. Growth hormone-releasing factor (GRF): physiological and biochemical studies with GRF preparations of bovine and porcine origin. Ann N Y Acad Sci. 1968 Feb 5;148(2):372–388. doi: 10.1111/j.1749-6632.1968.tb20364.x. [DOI] [PubMed] [Google Scholar]
  26. Schofield J. G. Role of cyclic 3',5'-adenosine monophosphate in the release of growth hormone in vitro. Nature. 1967 Sep 23;215(5108):1382–1383. doi: 10.1038/2151382b0. [DOI] [PubMed] [Google Scholar]
  27. Vergroesen A. J., De Boer J. Effects of prostaglandins E1 and F1-alpha on isolated frog and rat hearts in relation to the potassium-calcium ratio of the perfusion fluid. Eur J Pharmacol. 1968 Jun;3(3):171–176. doi: 10.1016/0014-2999(68)90128-3. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Wilber J. F., Utiger R. D. In vitro studies on mechanism of action of thyrotropin releasing factor. Proc Soc Exp Biol Med. 1968 Feb;127(2):488–490. doi: 10.3181/00379727-127-32722. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. 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]
  32. de Wied D., Witter A., Versteeg D. H., Mulder A. H. Release of ACTH by substances of central nervous system origin. Endocrinology. 1969 Sep;85(3):561–569. doi: 10.1210/endo-85-3-561. [DOI] [PubMed] [Google Scholar]

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