Skip to main content
SpringerLink
Log in

A possible role for endogenous opioids in the control of prolactin and luteinizing-hormone secretion in the human

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

We investigated the participation by endogenous opioid peptides in the control of prolactin and gonadotropin secretion in 5 normal men and 6 normal women, and in 4 men and 5 women with persisting hyperprolactinemia following transsphenoidal pituitary microsurgery for prolactinomas. Iv administration of the specific opiate-receptor antagonist, naloxone hydrochloride (0.2 mg/kg bolus), failed to affect serially sampled serum prolactin levels in normal male or female subjects. With prolactinoma patients, naloxone suppressed hyperprolactinemia to 37% and 32% of mean control values in 2 of 4 males, but in none of 6 females. When luteinizing hormone was serially sampled under the same conditions, 5 of 5 normal males (but no female, normal or abnormal) demonstrated a monophasic increase in serum LH concentrations after injection of the antagonist. The LH peak was 55 ± 4% above basal levels (p < 0.01). In contrast to normal men, only one of 4 hyperprolactinemic male patients manifested a stimulatory response of LH to naloxone. Among all 20 subjects, none exhibited a change in FSH levels acutely after naloxone. These data suggest that: i) naloxone will not fulfill its postulated role as an ideal therapy for hyperprolactinemia and hypogonadotropism, at least in women; ii) endogenous opioids may participate in the neuroendocrine regulation of LH secretion in the normal human; iii) male-female differences may modify the role of endogenous opioids; and iv) some male patients with hyperprolactinemia exhibit defective opioid-related neuroregulation of LH secretion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. MacLeod R.M. Regulation of prolactin secretion. In: Ganong, W.F., Martini, L. (Eds.), Frontiers in neu-roendocrinology. Raven Press, New York, 1976, vol. 4, p. 169.

    CAS  Google Scholar 

  2. Meites J., Bruni J.F., Van Vugt D.A., Smith A.F. Minireview — relation of endogenous opioid peptides and morphine to neuroendocrine function. Life Sci. 24: 1325, 1979.

    Article  CAS  PubMed  Google Scholar 

  3. Van Ree J.M., Versteeg D.H.G., Spaaphen-Kok W.B., DeWied D. Effects of morphine on hypothalamic noradrenaline and on pituitary-adrenal activity in rats. Neuroendocrinology 22: 305, 1976.

    Article  PubMed  Google Scholar 

  4. Rivier C., Vale W., Ling N., Brown M., Guillemin R. Stimulation in vivo of the secretion of prolactin and growth hormone by β-endorphin. Endocrinology 100: 238, 1977.

    Article  CAS  PubMed  Google Scholar 

  5. Cusan L., Dupont A., Kledzik S., Labrie L., Coy H., Schally A.V. Potent prolactin and growth-hormone releasing activity of more analogues of met-enkephalins. Nature 268: 254, 1977.

    Article  Google Scholar 

  6. Bruni J.F., Van Vugt D., Marshall S., Meites J. 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, 1977.

    Article  CAS  PubMed  Google Scholar 

  7. Tolis G, Hickey J., Guyda H. Effects of morphine on serum growth hormone, cortisol, prolactin, and thyroid stimulting hormone in man. J. Clin. Endocrinol. Metab. 41: 797, 1975.

    Article  CAS  PubMed  Google Scholar 

  8. Stubbs W.A., Jones A., Edwards C.R.W., Delitala G., Jeffcoate W.J., Ratter S.J. Hormonal and metabolic responses to an enkephalin analogue in normal man. Lancet 2: 1225, 1978.

    Article  CAS  PubMed  Google Scholar 

  9. Dent R.R., Tolis G. Methadone modulates pituitary growth hormone and prolactin secretion. 61st Annual Meeting of the Endocrine Society, Anaheim, CA, 1979, abstract no. 517.

    Google Scholar 

  10. Martini W.R. Opioid-antagonists. Pharmacol. Rev. 19: 463, 1976.

    Google Scholar 

  11. Székely J.I., Dunkai-Kovacs Z., Miglecz E., Ronai A.Z., Bajusz S. in vivo antagonism by naloxone of morphine, β — endorphin, and synthetic enkephalin analogues. J. Pharmacol. Exp. Ther. 207: 878, 1978.

    PubMed  Google Scholar 

  12. Morley J.E., Baranetsky NG., Carlson H.E., Hershman J.M., Varner A.A. Endocrine effects of naloxone. 60th Annual Meeting of the Endocrine Society, Miami, Florida, 1978, Abstract no. 401.

    Google Scholar 

  13. Tolis G., Ruggere D., Pinter E., Banovac K. Naloxone blockade of morphine-induced hyperprolactinemia and its ineffectiveness to modify basal prolactin secretion or its release by thyrotrophin (TSH)-releasing hormone or metochlopramide. 60th Annual Meeting of The Endocrine Society, Miami, Florida, 1978, Abstract no. 569.

    Google Scholar 

  14. Pang C.N. Bromley B., Zimmerman E. Effects of naloxone on plasma LH, FSH, prolactin and corticosterone levels in morphine-dependent ovariectomized rats. 61st Annual Meeting of the Endocrine Society, Anaheim, CA, 1979, Abstract no. 571.

    Google Scholar 

  15. Gold M.S., Redmond D.E., Donabedian R.F. The effects of opiate agonist and antagonist on serum prolactin in primates: possible role for endorphins in prolactin regulation. Endocrinology 105: 284, 1979.

    Article  CAS  PubMed  Google Scholar 

  16. Fine S.A., Frohman L.A. Loss of central-nervous-system component of dopaminergic inhibition of prolactin secretion in patients with prolactin-secreting tumors. J. Clin. Invest. 21: 973, 1978.

    Article  CAS  Google Scholar 

  17. Ferland L., Fuxe K., Eneroth P., Gustafsson J.A., Skett P. Effects of methionine-enkephalin on prolactin release and catecholamine levels and turnover in the median eminence. Eur. J. Pharmacol. 43: 89, 1977.

    Article  CAS  PubMed  Google Scholar 

  18. VanLoon G.R., Ho D., Kim C. β-endorphin-induced decrease in hypothalamic dopamine turnover. Endocrinology 106: 76, 1980.

    Article  CAS  Google Scholar 

  19. Cicero T.J., Schainker B.A, Meyer E.R. Endogenous opioids participate in the regulation of the hypothalamic-pituitary-luteinizing hormone axis and testosterone’s negative feedback control of luteinizing hormone. Endocrinology 104: 1286, 1979.

    Article  CAS  PubMed  Google Scholar 

  20. Pang C.N., Zimmerman E., Sawyer C.H. Morphine inhibition of the pre-ovulatory surges of plasma luteinizing hormone and follicle stimulating hormone in the rat. Endocrinology 101: 1726, 1977.

    Article  CAS  PubMed  Google Scholar 

  21. Muraki T., Nakadate H., Tokunaga Y., Kato R., Makino T. Effect of narcotic analgesics and naloxone or proestrus surges of LH, FSH and prolactin in rats. Neuroendocrinology 28: 241, 1979.

    Article  CAS  PubMed  Google Scholar 

  22. Agnati L.F., Benfenati F., Cortelli P., D’Allessandro R., Ghisoli E., Zampa G.A. A study of the effects of interaction between naloxone and 2-Br-α-ergocryptine or clonidine on LH, FSH, prolactin, and TSH levels in normal man serum. Neurosci. Lett. 12: 307, 1979.

    Article  CAS  PubMed  Google Scholar 

  23. Murray F.T., Osterman J., Sulewski J., Page R., Bergland R., Hammond J.M. Pituitary function following surgery for prolactinomas. Obstet. Gynecol. 54: 65, 1979.

    Article  CAS  PubMed  Google Scholar 

  24. Aubert J.L., Becker B.B., Raiti S. Report of the National Pituitary Agency collaborative study of the radioimmunoassay of prolactin. J. Clin. Endocrinol. Metab. 38: 1115, 1974.

    Article  CAS  PubMed  Google Scholar 

  25. Santen R.J., Bardin C.W. Episodic luteinizing-hormone secretion in man: pulse analysis, clinical interpretation, physiologic mechanisms. J. Clin. Invest. 52: 2617, 1973.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Winer B.J. Statistical principles in experimental design. McGraw-Hill Book Co., New York, 1971, p. 196.

    Google Scholar 

  27. Sawynok J., Pinsky C., LaBella F.S. Minireview: the specificity of naloxone as an opiate antagonist. Life Sci. 25: 1621, 1979.

    Article  CAS  PubMed  Google Scholar 

  28. Shin S.H. Blockade of ether-induced surge of prolactin by naloxone in male rats. Endocrinology 79: 397, 1978.

    Article  CAS  Google Scholar 

  29. Hart I.C., Cowie AT. Effect of morphine, naloxone, and an enkephalin analogue or plasma prolactin-growth hormone, insulin and thyroxine in goats. Clin. Endocrinol. (Oxf.) 10: 16P, 1978.

    Google Scholar 

  30. Rubin P., Swezey S., Blaschke T, Naloxone lowers plasma prolactin in man. Lancet 1: 1293, 1979.

    Article  CAS  PubMed  Google Scholar 

  31. Hardy J. Transsphenoidal surgery of hypersecreting pituitary tumors. In: Kohler P.O., Ross G.T. (Eds.), Diagnosis and treatment of pituitary tumors. American Elsevier, New York, 1973, p. 179.

    Google Scholar 

  32. Tolis G., Jukier L., Guyda H., Krieger D. Effect of naloxone on adrenocorticotrophin, growth hormone, and prolactin in patients with secretory pituitary tumors. Clin. Res. 27: 261 A, 1979 (Abstract).

    Google Scholar 

  33. Goodman R., Biller B., Moses A.C., Molitch M., Feldman Z., Post K. Restoration of normal prolactin secretory dynamics after surgical cure or prolactinomas is evidence against underlying hypothalamic dysregulation. 61st Annual Meeting of the Endocrine Society, Anaheim, CA, 1979, Abstract no. 348.

    Google Scholar 

  34. Blankstein J., Reyes F., Winter J., Faiman C. Failure of naloxone to alter growth hormone and prolactin levels in acromegalic and hyperprolactinemic patients. Clin. Endocrinol. (Oxf.) 11: 475, 1979.

    Article  CAS  Google Scholar 

  35. Quigley M.E., Sheehan K.L., Casper R.F., Yen S.S.C. Evidence for an increased opioid inhibition of LH secretion in hyperprolactinemic patients with pituitary microadenoma. J. Clin. Endocrinol. Metab. 50: 427, 1980.

    Article  CAS  PubMed  Google Scholar 

  36. Spampinato S., Locatelli V., Cocchi D., Vincenti L., Bajusz S., Ferri S., Muller E.E. Involvement of brain serotonin in the prolactin-releasing effects of opioid peptides. Endocrinology 105: 163, 1979.

    Article  CAS  PubMed  Google Scholar 

  37. Leiri T., Chen H.T., Meites J. Effects of morphine and naloxone on serum levels of luteinizing hormone and prolactin in prepubertal male and female rats. Neuroendocrinology 29: 288, 1979.

    Article  Google Scholar 

  38. Blank M.S., Panerai A.E., Friesen H.G. Opioid peptides modulate luteinzing hormone secretion during sexual maturation. Science 203: 1129, 1979.

    Article  CAS  PubMed  Google Scholar 

  39. Mirin S.M., Mendelson J.H., Ellingboe J., Myer R.E. Acute effects of heroin and naltrexone on testosterone and gonadotropin secretion: a pilot study. Psychoneuroendocrinology 1: 359, 1976.

    Article  Google Scholar 

  40. Mendelson J.H., Ellingboe J., Kuehnle J., Mello N.K. Effects of naltrexone on mood and neuroendocrine function in normal adult males. Psychoneuroendocrinology 3: 231, 1978.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, the Milton S. Hershey Medical Center, the Pennsylvania State University, Hershey, Pennsylvania, 17033, USA

    Johannes D. Veldhuis, T. J. Worgul & J. M. Hammond

  2. Department of Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA

    R. Monsaert

Authors
  1. Johannes D. Veldhuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. J. Worgul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Monsaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. M. Hammond
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by NIH Grant #HD10122 and Research Service Award # 1F32HD05755.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Veldhuis, J.D., Worgul, T.J., Monsaert, R. et al. A possible role for endogenous opioids in the control of prolactin and luteinizing-hormone secretion in the human. J Endocrinol Invest 4, 31–36 (1981). https://doi.org/10.1007/BF03349410

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03349410

Key-words

Search

Navigation