Pharmacological Studies of Pituitary Receptors Involved in the Control of Prolactin Secretion

  • Alain Enjalbert
  • Merle Ruberg
  • Sandor Arancibia
  • Mirette Priam
  • Claude Kordon
Part of the Biochemical Endocrinology book series (BIOEND)


The major action of the hypothalamus on mammalian prolactin secretion is inhibitory. Ectopic pituitary grafts (Everett, 1954; Meites et al., 1961), electrolytic lesion of the median eminence (Chen et al., 1970; Bishop et al., 1971) and in vitro incubation of adenohypophyseal tissue (Meites and Nicoll, 1966) result in increased prolactin secretion. It was postulated that the hypothalamus contained an unidentified factor that inhibited the release of prolactin at the hypophyseal level (Pasteels, 1961, 1967; Talwalker et al., 1963) and that this factor could reach the pituitary directly across the hypothalamo-hypophyseal portal system. This was substantiated by experiments in which hypothalamic extracts infused into a portal blood vessel induced a dose-dependent inhibition of prolactin release (Kamberi et al., 1971b). This inhibitory effect of hypothalamic extracts was found in many in vivo and in vitro preparations.


Vasoactive Intestinal Peptide Median Eminence Serum Prolactin Prolactin Secretion Prolactin Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anden, N. E., Dahlstrom, A., Fuxe, K., and Höckfelt, T., 1966, The effect of haloperidol and chlorpromazine on the amine levels of central monoamine neurons, Acta. Physiol. Scand. 68: 419.CrossRefGoogle Scholar
  2. Barnea, A., Ben-Jonathan, N., and Porter, J. C., 1976, Characterization of hypothalamic subcellular particles containing luteinizing hormone releasing hormone and thyrotropin releasing hormone, J. Neurochem. 27: 477.PubMedCrossRefGoogle Scholar
  3. Bauer, K., Graf, K. J., Faivre-Bauman, A., Beier, S., Tixier-Vidal, A., and Kleinkauf, H., 1978, Inhibition of prolactin secretion by histidyl proline diketopiperazine, Nature (London) 214: 114.Google Scholar
  4. Ben-David, M., Danon, A., and Sulman, F. G., 1970, Acute changes in blood and pituitary prolactin after a single injection of perphenazine, Neuroendocrinology 6: 336.PubMedCrossRefGoogle Scholar
  5. Ben-Jonathan, N., Olivier, C., Weiner, H. J., Mical, R. S., and Porter, J. C., 1977, Dopamine in hypophyseal portal plasma of the rat during the estrous cycle and throughout pregnancy, Endocrinology 100: 452.PubMedCrossRefGoogle Scholar
  6. Besson, J., Rotsztejn, W. H., Laburthe, M., Epelbaum, J., Beaudet, A., Kordon, C., and Rosselin, G., 1979, Vasoactive intestinal peptide (VIP): Brain distribution, subcellular localization and effect of deafferentation of the hypothalamus in male rats, Brain Res. 765: 79.CrossRefGoogle Scholar
  7. Birge, C. A., Jacobs, L. S., Hammer, C. T., and Daughaday, W. H., 1970, Catecholamine inhibition of prolactin secretion by isolated rat adenohypophysis, Endocrinology 86: 120.PubMedCrossRefGoogle Scholar
  8. Bishop, W., Krulich, L., Fawcett, L. P., and Me Cann, S. M., 1971, The effect of median eminence (ME) lesions on plasma levels of FSH, LH and prolactin in the rat, Proc. Soc. Exp. Biol. Med. 136: 925.PubMedGoogle Scholar
  9. Blake, C. A., 1974, Stimulation of pituitary prolactin and TSH release in lactating and proestrous rats, Endocrinology 94: 503.PubMedCrossRefGoogle Scholar
  10. Bockaert, J., Premont, J., Glowinski, J., Tassin, J. P., and Thierry, A. M., 1977, Topographical distribution and characteristics of dopamine and β adrenergic sensitive adenylate cyclase in the rat frontal cerebral cortex, striatum and substantia nigra, in Advances in Biochemical Psychopharmacology, Vol. 16 (E. Costa and G. L. Gessa, eds.), pp. 29–37, Raven Press, New YorkGoogle Scholar
  11. Boyd, A. E., III, Spencer, E., Jackson, I. M. D., and Reichlin, S., 1976, Prolactin-releasing-factor (PRF) in porcine hypothalamic extracts distinct from TRH, Endocrinology 99: 861.PubMedCrossRefGoogle Scholar
  12. Briaud, B., Enjalbert, A., Miale, C., and Kordon, C., 1979, Subcellular distribution of corticotropin releasing factor (CRF) in the medio-basal hypothalamus of the rat, Neuroendocrinology 28: 371.PubMedCrossRefGoogle Scholar
  13. Brown, G. M., Seeman, P., and Lee, T., 1976, Dopamine, neuroleptic receptors in basal hypothalamus and in pituitary, Endocrinology 99: 1407.PubMedCrossRefGoogle Scholar
  14. Bruni, J. F., Van Vugt, D., Marshall, S., and Meites, J., 1977, Effects of naloxone, morphine and methionine enkephalin on serum prolactin, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone, Life Sci. 21: 461.PubMedCrossRefGoogle Scholar
  15. Calabro, M. A., and MacLeod, R. M., 1978, Binding of dopamine to bovine anterior pituitary gland membranes, Neuroendocrinology 25: 32.PubMedCrossRefGoogle Scholar
  16. Chen, C. L., Amenomori, Y., Lu, K. H., Voogt, J. L., and Meites, J., 1970, Serum prolactin levels in rats with pituitary transplants or hypothalamic lesions, Neuroendocrinology 6: 220.PubMedCrossRefGoogle Scholar
  17. Chihara, K., Arimura, A., Coy, D. H., and Schally, A. V., 1978, Studies on the interaction of endorphin, substance P and endogenous somatostatin in growth hormone and prolactin release in rats, Endocrinology 102: 281.PubMedCrossRefGoogle Scholar
  18. Clemens, J. A., Smalstig, E. B., and Shaar, C. J., 1975, Inhibition of prolactin secretion by lergotrile mesylate: Mechanism of action, Acta Endocrinol. 70: 230.Google Scholar
  19. Creese, I., Schneider, R., and Snyder, S. H., 1977, 3H spiroperidol labels dopamine receptors in pituitary and brain, Eur. J. Pharmacol. 46: 377.PubMedCrossRefGoogle Scholar
  20. Cronin, M. J., Roberts, J. M., and Weiner, R. I., 1978, Dopamine and dihydroergocryptine binding to the anterior pituitary and other brain areas of the rat and sheep, Endocrinology 103: 302.PubMedCrossRefGoogle Scholar
  21. Dickerman, S., Kledzik, G., Gelato, M., Chen, H. J., and Meites, J., 1974, Effects of haloperidol on serum and pituitary prolactin LH and FSH and hypothalamic PIF and LRF, Neuroendocrinology 15: 10.PubMedCrossRefGoogle Scholar
  22. Donoso, A. O., Bishop, W., and McCann, S. M., 1973, The effects of drugs which modify catecholamine synthesis on serum prolactin in rats with median eminence lesions, Proc. Soc. Exp. Biol. Med. 143: 360.PubMedGoogle Scholar
  23. Donoso, A. O., Banzan, A. M., and Barcaglioni, J. C., 1974, Further evidence on the direct action of L-dopa on prolactin release, Neuroendocrinology 15: 236.PubMedCrossRefGoogle Scholar
  24. Dupont, A., Cusan, L., Labrie, F., Coy, D. H., and Hao-Li, C., 1977, Stimulation of prolactin release in the rat by intraventricular injection of β endorphin and methionine enkephalin, Biochem. Biophys. Res. Commun. 75: 76.PubMedCrossRefGoogle Scholar
  25. Enjalbert, A., Moos, F., Carbonell, L., Priam, M., and Kordon, C., 1977a, Prolactin inhibiting activity of dopamine free subcellular fractions from rat medio-basal hypothalamus, Neuroendocrinology 24: 147.PubMedCrossRefGoogle Scholar
  26. Enjalbert, A., Priam, M., and Kordon, C., 1977b, Evidence in favour of the existence of a dopamine free prolactin inhibiting factor (PIF) in rat hypothalamic extracts, Eur. J. Pharmacol. 41: 243.PubMedCrossRefGoogle Scholar
  27. Enjalbert, A., Ruberg, M., Fiore, L., and Kordon, C., 1978, Dopamine, GABA, PIF and in vitro regulation of prolactin secretion in the rat, Ann. Endocrinol. 39: 237.Google Scholar
  28. Enjalbert, A., Ruberg, M., Fiore, L., Arancibia, S., Priam, M., and Kordon, C., 1979a, Effect of morphine on the dopamine inhibition of pituitary prolactin release in vitro, Eur. J. Pharmacol. 53: 212.CrossRefGoogle Scholar
  29. Enjalbert, A., Ruberg, M., Fiore, L., Arancibia, S., Priam, M., and Kordon, C., 1979b, Independent inhibition of prolactin secretion by dopamine and gamma-amino-butyric acid in vitro, Endocrinology 105: 823.PubMedCrossRefGoogle Scholar
  30. Enjalbert, A., Ruberg, M., Arancibia, S., Priam, M., and Koron, C., 1979c, Endogenous opiates block dopamine inhibition of prolactin secretion in vitro, Nature 280: 595.PubMedCrossRefGoogle Scholar
  31. Epelbaum, J., Brazeau, P., Tsang, D., Brawer, J., and Martin, J. B., 1977, Subcellular distribution of radioimmunoas say able somatostatin in rat brain, Brain Res. 126: 309.PubMedCrossRefGoogle Scholar
  32. Everett, J. W., 1954, Luteotrophic function of autografts of the rat hypophysis, Endocrinology 54: 685.PubMedCrossRefGoogle Scholar
  33. Ferland, L., Fuxe, K., Eweroth, P., Gustafsson, J. A., and Skett, P., 1977, Effects of methionine-enkephalin on prolactin release and catecholamine levels and turnover in the median eminence, Eur. J. Pharmacol. 43: 89.PubMedCrossRefGoogle Scholar
  34. Gautvik, K. M., Tashjian, A. H., Jr, Kourides, I. A., Weintraub, B. D., Graeber, C. T., Maloof, F., Suzuki, K., and Zuckerman, J. E., 1974, Thyrotropin-releasing hormone is not sole physiologic mediator of prolactin release during suckling, N. Engl. J. Med. 290: 1162.PubMedCrossRefGoogle Scholar
  35. Gibbs, D. M., and Neill, J. D., 1978, Dopamine levels in hypophyseal stalk blood in the rat are sufficient to inhibit prolactin secretion in vivo, Endocrinology 102: 1895.PubMedCrossRefGoogle Scholar
  36. Gourdji, D., and Tixier-Vidal, A., 1966, Mise en évidence d’un contrôle hypothalamique stimulant de la prolactine hypophysaire chez le canard, C. R. Acad. Sci. 263: 162.Google Scholar
  37. Gourdji, D., Kerdelhue, B., and Tixier-Vidal, A., 1966, Mise en évidence d’un clone de cellules hypophysaires sécrétant de la prolactine (clone GH3): Modification induite par l’hormone de libération de l’hormone thyrotrope TRF, C. R. Acad. Sci. 274: 437.Google Scholar
  38. Grandison, L., and Guidotti, A., 1977, Regulation of prolactin release by endogenous opiates, Nature (London) 270: 357.CrossRefGoogle Scholar
  39. Greibrokk, T., Currie, B. L., Johansson, K. N. G., Hansen, J. J., and Foikers, K., 1974, Purification of a prolactin inhibiting hormone and the revealing of hormone D-GHIH which inhibits the release of growth-hormone, Biochem. Biophys. Res. Commun. 59: 704.PubMedCrossRefGoogle Scholar
  40. Greibrokk, T., Hansen, J., Knudsen, R., Lam, Y. K., and Foikers, K., 1975, On the isolation of a prolactin inhibiting factor (hormone), Biochem. Biophys. Res. Commun. 67: 338.PubMedCrossRefGoogle Scholar
  41. Hill-Samli, M., and MacLeod, R. M., 1974, Interaction of thyrotropin-releasing hormone and dopamine on the release of prolactin from the rät anterior pituitary in vitro, Endocrinology 95: 1189.PubMedCrossRefGoogle Scholar
  42. Hill-Samli, M., and MacLeod, R. M., 1975, TRH blockade of the ergocryptine and apomorphine inhibition of prolactin release in vitro, Proc. Soc. Exp. Biol. Med. 149: 511.PubMedGoogle Scholar
  43. Höckfelt, T., 1967, The possible ultrastructural identification of tuberoinfundibular dopa-mine-containing nerve-endings in the median eminence of the rat, Brain Res. 5: 121.CrossRefGoogle Scholar
  44. Iversen, L. L., 1975, Dopamine receptors in the brain, Science 4193: 1084.CrossRefGoogle Scholar
  45. Jimenez, A. E., Voogt, J. L., and Carr, L. A., 1978, L-3,4-Dihydroxyphenylalanine (L-dopa) as an inhibitor of prolactin release, Endocrinology 102: 166.PubMedCrossRefGoogle Scholar
  46. Kamberi, I. A., Mical, R. S., and Porter, J. L., 1971a, Effect of anterior pituitary perfusion and intraventricular injection of catecholamines on prolactin release, Endocrinology 88: 1012.PubMedCrossRefGoogle Scholar
  47. Kamberi, I. A., Mical, R. S., and Porter, J. L., 1971b, Pituitary portal vessels infusion of hypothalamic extract and release of LH, FSH and prolactin, Endocrinology 88: 1294.PubMedCrossRefGoogle Scholar
  48. Kato, Y., Iwasaki, Y., Iwasaki, J., Abe, H., Yanaihara, N., and Imura, H., 1978, Prolactin release by vasoactive intestinal polypeptide in rats, Endocrinology 103: 554.PubMedCrossRefGoogle Scholar
  49. Koch, Y., Lu, K. H., and Meites, J., 1970, Biphasic effect of catecholamines on pituitary prolactin release in vitro, Endocrinology 87: 673.PubMedCrossRefGoogle Scholar
  50. Kragt, C., and Meites, J., 1965, Stimulation of pigeon pituitary prolactin release by pigeon hypothalamic extracts in vitro, Endocrinology 76: 1169.PubMedCrossRefGoogle Scholar
  51. Labrie, F., Beaulieu, M., Caron, M. G., and Raymond, V., 1978, The adenohypophyseal dopamine receptor specificity and modulation of its activity by estradol, in: Progress in Prolactin Physiology and Pathology (C. Robyn and M. Harter, eds.), pp. 121–136, Elsever North-Holland, Amsterdam.Google Scholar
  52. Lu, K. H., and Meites, J., 1972, Effects of L-dopa on serum prolactin and PIF in intact and hypophysectomized pituitary grafted rats, Endocrinology 91: 868.PubMedCrossRefGoogle Scholar
  53. Lu, K. H., Amenomori, Y., Chen, C., and Meites, J., 1970, Effects of central acting drugs on serum and pituitary prolactin levels in rats, Endocrinology 87: 667.PubMedCrossRefGoogle Scholar
  54. Maanen, J. H., and Smelik, P. G., 1968, Induction of pseudopregnancy in rat following local depletion of monoamine in the median eminence of the hypothalamus, Neuroen-docrinology 3: 177.CrossRefGoogle Scholar
  55. MacLeod, R.M., 1969, Influence of norepinephrine and catecholamines depleting agents on the synthesis and release of prolactin and growth hormone, Endocrinology 85: 916.PubMedCrossRefGoogle Scholar
  56. MacLeod, R. M., and Lehmeyer, J. E., 1974, Studies on the mechanism of dopamine-mediated inhibition of prolactin secretion, Endocrinology 94: 1077.PubMedCrossRefGoogle Scholar
  57. McLennan, M., and York, D. H., 1973, Gamma-aminobutyric acid antagonists in Crustacea, Can. J. Physiol. Pharmacol. 51: 774.PubMedCrossRefGoogle Scholar
  58. Meites, J., and Clemens, J., 1972, Hypothalamic control of prolactin secretion, Vitam. Horm. (N. Y.) 30: 165.CrossRefGoogle Scholar
  59. Meites, J., and Nicoll, C. S., 1966, Adenohypophyseal prolactin, Annu. Rev. Physiol. 28: 57.PubMedCrossRefGoogle Scholar
  60. Meites, J., Kahn, R. H., and Nicoll, C. S., 1961, Prolactin production by rat pituitary expiants in vitro, Proc. Soc. Exp. Biol. Med. 108: 440.Google Scholar
  61. Mueller, G. P., Chen, H. J., and Meites, J., 1973, In vivo stimulation of prolactin release in the rat by synthetic TRH, Proc. Soc. Exp. Biol. Med. 144: 613.PubMedGoogle Scholar
  62. Nakano, H., Fawcett, C. P., and McCann, S. M., 1976, Enzymatic dissociation and short-term culture of isolated rat anterior pituitary cells for studies on the control of hormone secretion, Endocrinology 98: 278.PubMedCrossRefGoogle Scholar
  63. Noel, G. L., Dimond, R. C., Wartofsky, L., Earll, J. M., and Frantz, A. G., 1974, Studies of prolactin and FSH secretion by continuous infusion of small amounts of thyrotro-phin-releasing hormone (TRH), J. Clin. Endocrinol. Metab. 39: 6.PubMedCrossRefGoogle Scholar
  64. Ojeda, S. R., Harms, P. G., and McCann, S. M., 1974, Effect of blockade of dopaminergic receptors on prolactin and LH release: Median eminence and pituitary sites of action, Endocrinology 94: 1650.CrossRefGoogle Scholar
  65. Ondo, J. G., and Pass, K. A., 1976, The effects of neurally active amino-acids on prolactin secretion, Endocrinology 98: 1248.PubMedCrossRefGoogle Scholar
  66. Pasteels, J. L., 1961, Premiers résultats de cultures combinées in vitro d’hypophyses et d’hypothalamus dans le but d’apprécier la production de prolactine, C. R. Acad. Sci. 253: 3074.Google Scholar
  67. Pasteels, J. L., 1967, Contrôle de la sécrétion de prolactine par le système nerveux, Arch. Anat. Microsc. Morphol. Exp. 56: 530.PubMedGoogle Scholar
  68. Plotsky, P. M., Gibbs, D. M., and Neill, J. D., 1978, Liquid Chromatographie electrochemical measurement of dopamine in hypophyseal stalk blood of rats, Endocrinology 102: 1877.CrossRefGoogle Scholar
  69. Ramirez, V. D., Gautron, J. P., Epelbaum, J., Pattou, E., Zamora, A., and Kordon, C., 1975, Distribution of LH-RH in subcellular fractions of medio-basal hypothalamus, Mol. Cell. Endocrinol. 3: 339.PubMedCrossRefGoogle Scholar
  70. Rivier, C., and Vale, W., 1977, Effects of gamma-aminobutyric acid and histamine on prolactin secretion in the rat, Endocrinology 101: 506.PubMedCrossRefGoogle Scholar
  71. River, C., Brown, M., and Vale, W., 1977a, Effect of neurotensin, substance P and morphine sulfate on the secretion of PRL and growth hormone in the rat, Endocrinology 100: 751.CrossRefGoogle Scholar
  72. River, C., Vale, W., Ling, N., Brown, M., and Guillemin, R., 1977b, Stimulation in vivo of the secretion of prolactin and growth hormone by β endorphin, Endocrinology 100: 238.CrossRefGoogle Scholar
  73. Ruberg, M., Rotsztejn, W. H., Arancibia, S., Besson, J., and Enjalbert, A., 1978, Stimulation of prolactin release by vasoactive intestinal peptide (VIP), Eur. J. Pharmacol. 51: 319.PubMedCrossRefGoogle Scholar
  74. Schally, A. V., Dupont, A., Arimura, A., Takahara, J., Redding, T. W., Clemens, J., and Shaar, C., 1976, Purification of a catecholamine-rich fraction with prolactin release inhibiting factor (PIF) activity from porcine hypothalami, Acta. Endocrinol. 82: 1.PubMedGoogle Scholar
  75. Schally, A. V., Redding, T. W., Arimura, A., Dupont, A., and Linthicum, G. L., 1977, Isolation of gamma-aminobutyric acid from pig hypothalami and demonstration of its prolactin release inhibiting (PIF) activity in vivo and in vitro, Endocrinology 100: 681.PubMedCrossRefGoogle Scholar
  76. Shaar, C. J., and Clemens, J. A., 1974, The role of catecholamines in the release of anterior pituitary prolactin m vitro, Endocrinology 95: 1202.PubMedCrossRefGoogle Scholar
  77. Shaar, C. J., Frederickson, R. C. A., Dininger, N. B., and Jackson, L., 1977, Enkephalin analogues and naloxone modulate the release of growth hormone and prolactin: Evidence for regulation by an endogenous opioid peptide in brain, Life Sci. 21: 853.PubMedCrossRefGoogle Scholar
  78. Shin, S. M., Morris, A., Snyder, J., Hymes, W. C., and Milligan, J. V., 1974, Subcellular localization of LH-RH in the rat hypothalamus, Neuroendocrinology 16: 191.PubMedCrossRefGoogle Scholar
  79. Smalstig, E. B., Sawyer, B. D., and Clemens, J. A., 1974, Inhibition of rat prolactin release by apomorphine in vivo and in vitro, Endocrinology 95: 123.PubMedCrossRefGoogle Scholar
  80. Taber, C. A., and Karavolas, H. J., 1974, Subcellular localization of LH releasing activity in the rat hypothalamus, Endocrinology 96: 446.CrossRefGoogle Scholar
  81. Takahara, J., Arimura, A., and Schally, A. V., 1974, Suppression of prolactin release by a purified porcine PIF preparation and catecholamines infused into a rat hypophyseal portal vessel, Endocrinology 95: 462.PubMedCrossRefGoogle Scholar
  82. Talwalker, P. K., Ratner, A., and Meites, J., 1963, In vitro inhibition of pituitary prolactin synthesis and release by hypothalamic extracts, Am. J. Physiol. 205: 213.PubMedGoogle Scholar
  83. Tappaz, M. L., Brownstein, M. J., and Kopin, I. J., 1977, Glutamate decarboxylase (GAD) and gamma aminobutyric acid (GABA) in discrete nuclei of hypothalamus and substantia nigra, Brain Red. 125: 109.CrossRefGoogle Scholar
  84. Tashjian, A. H., Barousky, N. J., and Jensen, D. K., 1971, Thyrotropin releasing hormone: Direct evidence for stimulation of prolactin production by pituitary cell in culture, Biochem. Biophys. Res. Commun. 43: 516.PubMedCrossRefGoogle Scholar
  85. Valverde, R. C., Chieffo, V., and Reichlin, S., 1972, Prolactin releasing factor in porcine and rat hypothalamic tissue, Endocrinology 91: 982.PubMedCrossRefGoogle Scholar
  86. Van Vugt, D. A., Bruni, J. F., and Meites, J., 1978, Naloxone inhibition of stress-induced increase in prolactin secretion, Life Sci. 22: 85.PubMedCrossRefGoogle Scholar
  87. Vijayan, E., and McCann, S. M., 1978, The effect of systemic administration of dopamine and apomorphine on plasma LH and prolactin concentrations in conscious rats, Neuroendocrinology 25: 221.PubMedCrossRefGoogle Scholar
  88. Weiner, R. I., 1975, Role of brain catecholamines in the control of LH and prolactin secretion, in: Hypothalamic Hormones (M. Motta, P. G. Grosignani, and L. Martini, eds.), p. 249, Academic Press, London.Google Scholar
  89. Weiner, R. I., Shryne, J. E., Gorski, R. A., and Sawyer, C. H., 1972, Changes in the catecholamine content of the rat hypothalamus following deafferentation, Endocrinology 90: 867.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1980

Authors and Affiliations

  • Alain Enjalbert
    • 1
  • Merle Ruberg
    • 1
  • Sandor Arancibia
    • 1
  • Mirette Priam
    • 1
  • Claude Kordon
    • 1
  1. 1.Unite 159 de NeuroendocrinologieCentre Paul Broca de l’INSERMParisFrance

Personalised recommendations