Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 Jan;73(1):66–78. doi: 10.1172/JCI111208

Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

M Ishibashi, T Yamaji
PMCID: PMC424971  PMID: 6140273

Abstract

To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)1 and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed. This inhibition was blocked by D2 receptor blockade with metoclopramide or sulpiride, but not by D1 receptor blockade. Similarly, dopamine suppressed GH and PRL release by nonadenomatous pituitary cells in a dose-dependent manner, which was again blocked by D2 receptor blockade. The minimum effective concentration of dopamine required for a significant inhibition of PRL secretion (0.01 microM) was lower than that for GH release (0.1 microM). Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells. This effect was blocked by sulpiride, phentolamine, however, was ineffective. When TRH was added to the media, both GH and PRL secretion were enhanced in adenoma cells, while only the stimulation of PRL release was observed in nonadenomatous pituitary cells. Coincubation of TRH and dopamine resulted in variable effects on GH and PRL secretion. Somatostatin consistently lowered GH and PRL secretion in both adenomatous and nonadenomatous pituitary cells and completely blocked the TRH-induced stimulation of GH and PRL secretion from adenoma cells. Opioid peptides (1 microM) failed to affect hormone release. These results suggest that no qualitative difference in GH and PRL responses to dopaminergic agonists or to somatostatin exists between adenoma cells of acromegalic patients and normal pituitary cells, and that the direct effect of catecholamines on GH and PRL secretion from human pituitary cells is mediated mainly through dopamine receptor activation.

Full text

PDF
67

Selected References

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

  1. Adams E. F., Brajkovich I. E., Mashiter K. Growth hormone and prolactin secretion by dispersed cell cultures of a normal human pituitary: effects of thyrotrophin releasing hormone, theophylline, somatostatin, and 2-bromo-alpha-ergocryptine. Acta Endocrinol (Copenh) 1981 Nov;98(3):345–351. doi: 10.1530/acta.0.0980345. [DOI] [PubMed] [Google Scholar]
  2. Adams E. F., Brajkovich I. E., Mashiter K. Hormone secretion by dispersed cell cultures of human pituitary adenomas: effects of theophylline, thyrotropin-releasing hormone, somatostatin, and 2-bromo-alpha-ergocryptine. J Clin Endocrinol Metab. 1979 Jul;49(1):120–126. doi: 10.1210/jcem-49-1-120. [DOI] [PubMed] [Google Scholar]
  3. Ben-Jonathan N., Oliver C., Weiner H. J., Mical R. S., Porter J. C. Dopamine in hypophysial portal plasma of the rat during the estrous cycle and throughout pregnancy. Endocrinology. 1977 Feb;100(2):452–458. doi: 10.1210/endo-100-2-452. [DOI] [PubMed] [Google Scholar]
  4. Boyd A. E., 3rd, Lebovitz H. E., Pfeiffer J. B. Stimulation of human-growth-hormone secretion by L-dopa. N Engl J Med. 1970 Dec 24;283(26):1425–1429. doi: 10.1056/NEJM197012242832602. [DOI] [PubMed] [Google Scholar]
  5. Bression D., Brandi A. M., Nousbaum A., Le Dafniet M., Racadot J., Peillon F. Evidence of dopamine receptors in human growth hormone (GH)-secreting adenomas with concomitant study of dopamine inhibition of GH secretion in a perifusion system. J Clin Endocrinol Metab. 1982 Sep;55(3):589–593. doi: 10.1210/jcem-55-3-589. [DOI] [PubMed] [Google Scholar]
  6. Camanni F., Massara F., Belforte L., Molinatti G. M. Changes in plasma growth hormone levels in normal and acromegalic subjects following administration of 2-bromo-alpha-ergocryptine. J Clin Endocrinol Metab. 1975 Mar;40(3):363–366. doi: 10.1210/jcem-40-3-363. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Chiodini P. G., Liuzzi A., Muller E. E., Botalla L., Cremascoli G., Oppizzi G., Verde G., Silvestrini F. Inhibitory effect of an ergoline derivative, methergoline, on growth hormone and prolactin levels in acromegalic patients. J Clin Endocrinol Metab. 1976 Aug;43(2):356–363. doi: 10.1210/jcem-43-2-356. [DOI] [PubMed] [Google Scholar]
  9. Cryer P. E., Daughaday W. H. Adrenergic modulation of growth hormone secretion in acromegaly: alpha- and beta-adrenergic blockade produce qualitatively normal responses but no effect on L-dopa suppresion. J Clin Endocrinol Metab. 1977 May;44(5):977–979. doi: 10.1210/jcem-44-5-977. [DOI] [PubMed] [Google Scholar]
  10. Cryer P. E., Daughaday W. H. Adrenergic modulation of growth hormone secretion in acromegaly: suppression during phentolamine and phentolamine-isoproterenol administration. J Clin Endocrinol Metab. 1974 Oct;39(4):658–663. doi: 10.1210/jcem-39-4-658. [DOI] [PubMed] [Google Scholar]
  11. Dannies P. S., Rudnick M. S. 2-Bromo-alpha-ergocryptine causes degradation of prolactin in primary cultures of rat pituitary cells after chronic treatment. J Biol Chem. 1980 Apr 10;255(7):2776–2781. [PubMed] [Google Scholar]
  12. Denef C., Manet D., Dewals R. Dopaminergic stimulation of prolactin release. Nature. 1980 May 22;285(5762):243–246. doi: 10.1038/285243a0. [DOI] [PubMed] [Google Scholar]
  13. Dupont A., Cusan L., Garon M., Labrie F., Li C. H. Beta-endorphin: stimulation of growth hormone release in vivo. Proc Natl Acad Sci U S A. 1977 Jan;74(1):358–359. doi: 10.1073/pnas.74.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Enjalbert A., Ruberg M., Arancibia S., Priam M., Kordon C. Endogenous opiates block dopamine inhibition of prolactin secretion in vitro. Nature. 1979 Aug 16;280(5723):595–597. doi: 10.1038/280595a0. [DOI] [PubMed] [Google Scholar]
  15. Feldman J. M., Plonk J. W., Bivens C. H. Inhibitory effect of serotonin antagonists on growth hormone release in acromegalic patients. Clin Endocrinol (Oxf) 1976 Jan;5(1):71–78. [PubMed] [Google Scholar]
  16. Frohman L. A., Burek L., Stachura M. A. Characterization of growth hormone of different molecular weights in rat, dog and human pituitaries. Endocrinology. 1972 Jul;91(1):262–269. doi: 10.1210/endo-91-1-262. [DOI] [PubMed] [Google Scholar]
  17. Gibbs D. M., Neill J. D. Dopamine levels in hypophysial stalk blood in the rat are sufficient to inhibit prolactin secretion in vivo. Endocrinology. 1978 Jun;102(6):1895–1900. doi: 10.1210/endo-102-6-1895. [DOI] [PubMed] [Google Scholar]
  18. Grossman A., Clement-Jones V. Opiate receptors: enkephalins and endorphins. Clin Endocrinol Metab. 1983 Mar;12(1):31–56. doi: 10.1016/s0300-595x(83)80028-0. [DOI] [PubMed] [Google Scholar]
  19. Hall R., Besser G. M., Schally A. V., Coy D. H., Evered D., Goldie D. J., Kastin A. J., McNeilly A. S., Mortimer C. H., Phenekos C. Action of growth-hormone-release inhibitory hormone in healthy men and in acromegaly. Lancet. 1973 Sep 15;2(7829):581–584. doi: 10.1016/s0140-6736(73)92413-6. [DOI] [PubMed] [Google Scholar]
  20. Irie M., Tsushima T. Increase of serum growth hormone concentration following thyrotropin-releasing hormone injection in patients with acromegaly or gigantism. J Clin Endocrinol Metab. 1972 Jul;35(1):97–100. doi: 10.1210/jcem-35-1-97. [DOI] [PubMed] [Google Scholar]
  21. Ishibashi M., Yamaji T. Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro. J Clin Invest. 1981 Oct;68(4):1018–1027. doi: 10.1172/JCI110324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ishibashi M., Yamaji T. Effect of thyrotropin-releasing hormone and bromoergocriptine on growth hormone and prolactin secretion in perfused pituitary adenoma tissues of acromegaly. J Clin Endocrinol Metab. 1978 Dec;47(6):1251–1256. doi: 10.1210/jcem-47-6-1251. [DOI] [PubMed] [Google Scholar]
  23. Ishibashi M., Yamaji T., Kosaka K. Effect of bromoergocriptine on TRH-induced growth hormone and prolactin release in acromegalic patients. J Clin Endocrinol Metab. 1977 Aug;45(2):275–279. doi: 10.1210/jcem-45-2-275. [DOI] [PubMed] [Google Scholar]
  24. Ishibashi M., Yamaji T., Kosaka K. Induction of growth hormone and prolactin secretion by luteinizing hormone-releasing hormone and its blockade by bromoergocriptine in acromegalic patients. J Clin Endocrinol Metab. 1978 Aug;47(2):418–421. doi: 10.1210/jcem-47-2-418. [DOI] [PubMed] [Google Scholar]
  25. Kebabian J. W., Calne D. B. Multiple receptors for dopamine. Nature. 1979 Jan 11;277(5692):93–96. doi: 10.1038/277093a0. [DOI] [PubMed] [Google Scholar]
  26. Lal S., De la Vega C. E., Sourkes T. L., Friesen H. G. Effect of apomorphine on human-growth-hormone secretion. Lancet. 1972 Sep 23;2(7778):661–661. doi: 10.1016/s0140-6736(72)93061-9. [DOI] [PubMed] [Google Scholar]
  27. Lawton N. F., Evans A. J., Weller R. O. Dopaminergic inhibition of growth hormone and prolactin release during continuous in vitro perifusion of normal and adenomatous human pituitary. J Neurol Sci. 1981 Feb;49(2):229–239. doi: 10.1016/0022-510x(81)90081-2. [DOI] [PubMed] [Google Scholar]
  28. Leebaw W. F., Lee L. A., Woolf P. D. Dopamine affects basal and augmented pituitary hormone secretion. J Clin Endocrinol Metab. 1978 Sep;47(3):480–487. doi: 10.1210/jcem-47-3-480. [DOI] [PubMed] [Google Scholar]
  29. Liuzzi A., Chiodini P. G., Botalla L., Cremascoli G., Müller E. E., Silvestrini F. Decreased plasma growth hormone (GH) levels in acromegalics following CB 154(2-Br-alpha ergocryptine) administration. J Clin Endocrinol Metab. 1974 May;38(5):910–912. doi: 10.1210/jcem-38-5-910. [DOI] [PubMed] [Google Scholar]
  30. Liuzzi A., Chiodini P. G., Botalla L., Cremascoli G., Silvestrini F. Inhibitory effect of L-Dopa on GH release in acromegalic patients. J Clin Endocrinol Metab. 1972 Dec;35(6):941–943. doi: 10.1210/jcem-35-6-941. [DOI] [PubMed] [Google Scholar]
  31. Mains R. E., Eipper B. A. Biosynthesis of adrenocorticotropic hormone in mouse pituitary tumor cells. J Biol Chem. 1976 Jul 10;251(13):4115–4120. [PubMed] [Google Scholar]
  32. Neill J. D., Frawley L. S., Plotsky P. M., Tindall G. T. Dopamine in hypophysial stalk blood of the rhesus monkey and its role in regulating prolactin secretion. Endocrinology. 1981 Feb;108(2):489–494. doi: 10.1210/endo-108-2-489. [DOI] [PubMed] [Google Scholar]
  33. Nishikori K., Noshiro O., Sano K., Maeno H. Characterization, solubilization, and separation of two distinct dopamine receptors in canine caudate nucleus. J Biol Chem. 1980 Nov 25;255(22):10909–10915. [PubMed] [Google Scholar]
  34. Peillon F., Cesselin F., Bression D., Zygelman N., Brandi A. M., Nousbaum A., Mauborgne A. In vitro effect of dopamine and L-dopa on prolactin and growth hormone release from human pituitary adenomas. J Clin Endocrinol Metab. 1979 Nov;49(5):737–741. doi: 10.1210/jcem-49-5-737. [DOI] [PubMed] [Google Scholar]
  35. Rivier C., Vale W., Ling N., Brown M., Guillemin R. Stimulation in vivo of the secretion of prolactin and growth hormone by beta-endorphin. Endocrinology. 1977 Jan;100(1):238–241. doi: 10.1210/endo-100-1-238. [DOI] [PubMed] [Google Scholar]
  36. Sachdev Y., Gomez-Pan A., Tunbridge W. M., Duns A., Weightman D. R., Hall R., Goolamali S. K. Bromocriptine therapy in acromegaly. Lancet. 1975 Dec 13;2(7946):1164–1168. doi: 10.1016/s0140-6736(75)92655-0. [DOI] [PubMed] [Google Scholar]
  37. Schalch D. S., Gonzalez-Barcena D., Kastin A. J., Schally A. V., Lee L. A. Abnormalities in the release of TSH in response to thyrotropin-releasing hormone (TRH) in patients with disorders of the pituitary, hypothalamus and basal ganglia. J Clin Endocrinol Metab. 1972 Oct;35(4):609–615. doi: 10.1210/jcem-35-4-609. [DOI] [PubMed] [Google Scholar]
  38. Shaar C. J., Clemens J. A. The role of catecholamines in the release of anterior pituitary prolactin in vitro. Endocrinology. 1974 Nov;95(5):1202–1212. doi: 10.1210/endo-95-5-1202. [DOI] [PubMed] [Google Scholar]
  39. Shaar C. J., Frederickson R. C., Dininger N. B., Jackson L. Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin--evidence for regulation by an endogenous opioid peptide in brain. Life Sci. 1977 Sep 15;21(6):853–860. doi: 10.1016/0024-3205(77)90415-5. [DOI] [PubMed] [Google Scholar]
  40. Siler T. M., VandenBerg G., Yen S. S., Brazeau P., Vale W., Guillemin R. Inhibition of growth hormone release in humans by somatostatin. J Clin Endocrinol Metab. 1973 Oct;37(4):632–634. doi: 10.1210/jcem-37-4-632. [DOI] [PubMed] [Google Scholar]
  41. Tallo D., Malarkey W. B. Adrenergic and dopaminergic modulation of growth hormone and prolactin secretion in normal and tumor bearing human pituitaries in monolayer culture. J Clin Endocrinol Metab. 1981 Dec;53(6):1278–1284. doi: 10.1210/jcem-53-6-1278. [DOI] [PubMed] [Google Scholar]
  42. Thorner M. O., Chait A., Aitken M., Benker G., Bloom S. R., Mortimer C. H., Sanders P., Mason A. S., Besser G. M. Bromocriptine treatment of acromegaly. Br Med J. 1975 Feb 8;1(5953):299–303. doi: 10.1136/bmj.1.5953.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tolis G., Dent R., Guyda H. Opiates, prolactin, and the dopamine receptor. J Clin Endocrinol Metab. 1978 Jul;47(1):200–203. doi: 10.1210/jcem-47-1-200. [DOI] [PubMed] [Google Scholar]
  44. Wass J. A., Thorner M. O., Morris D. V., Rees L. H., Mason A. S., Jones A. E., Besser G. M. Long-term treatment of acromegaly with bromocriptine. Br Med J. 1977 Apr 2;1(6065):875–878. doi: 10.1136/bmj.1.6065.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Woolf P. D., Lantigua R., Lee L. A. Dopamine inhibition of stimulated growth hormone secretion: evidence for dopaminergic modulation of insulin- and L-dopa-induced growth hormone secretion in man. J Clin Endocrinol Metab. 1979 Sep;49(3):326–330. doi: 10.1210/jcem-49-3-326. [DOI] [PubMed] [Google Scholar]
  46. Yamaji T., Ishibashi M., Katayama S., Itabashi A., Ohsawa N., Kondo Y., Mizumoto Y., Kosaka K. Neurophysin biosynthesis in vitro in oat cell carcinoma of the lung with ectopic vasopressin production. J Clin Invest. 1981 Dec;68(6):1441–1449. doi: 10.1172/JCI110396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yamaji T., Ishibashi M., Kosaka K., Fukushima T., Hori T., Manaka S., Sano K. Pituitary apoplexy in acromegaly during bromocriptine therapy. Acta Endocrinol (Copenh) 1981 Oct;98(2):171–177. doi: 10.1530/acta.0.0980171. [DOI] [PubMed] [Google Scholar]
  48. Yamaji T., Shimamoto K., Ishibashi M., Kosaka K., Orimo H. Effect of age and sex on circulating and pituitary prolactin levels in human. Acta Endocrinol (Copenh) 1976 Dec;83(4):711–719. doi: 10.1530/acta.0.0830711. [DOI] [PubMed] [Google Scholar]
  49. Yen S. S., Siler T. M., DeVane G. W. Effect of somatostatin in patients with acromegaly: suppression of growth hormone, prolactin, insulin and glucose levels. N Engl J Med. 1974 Apr 25;290(17):935–938. doi: 10.1056/NEJM197404252901704. [DOI] [PubMed] [Google Scholar]
  50. von Graffenried B., del Pozo E., Roubicek J., Krebs E., Poldinger W., Burmeister P., Kerp L. Effects of the synthetic enkephalin analogue FK 33-824 in man. Nature. 1978 Apr 20;272(5655):729–730. doi: 10.1038/272729a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES