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Lack of effect of the dopamine D1 antagonist, NNC 01-0687, on unstimulated and stimulated release of anterior pituitary hormones in males

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Abstract

Dopamine in humans inhibits the secretion of luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH) and prolactin (PRL), and is a stimulator of growth hormone (GH) secretion. Dopamine-D1 receptor stimulation with fenoldopam increases basal PRL levels, suppresses TSH, and increases gonadotropin releasing hormone (LHRH) induced LH release. We have investigated the effect of a dopamine D1-receptor antagonist, NNC 01-0687, on the secretion of anterior pituitary hormones. In 8 healthy males NNC 01-0687 and placebo were administered orally in a double-blind placebo controlled cross-over study for three days with a wash-out period of 14 days. Hormonal responses (PRL, LH, FSH, GH, TSH, thyroid hormones and testosterone), unstimulated and LHRH/TRH stimulated, were studied on days 1 and 3. No significant difference (p>0.05) between placebo and active periods was found neither in unstimulated nor in stimulated hormone concentrations expressed in absolute values, percent change of before, incremental values and area under the curve. These results suggest that the neuronal DA-D1 activity is not activated during basal conditions in healthy male subjects.

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References

  1. Leebaw W.F., Lee LA, Woolf P.D. Dopamine affects basal and augmented pituitary hormone secretion. J. Clin. Endocrinol. Metab. 47: 480, 1978.

    Article  PubMed  CAS  Google Scholar 

  2. 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  PubMed Central  PubMed  CAS  Google Scholar 

  3. Strange P.G. New insights into dopamine receptors in the central nervous system. Neurochem. Int. 22: 223, 1993.

    Article  PubMed  CAS  Google Scholar 

  4. Kebabian J.W. Brain dopamine receptors: 20 years of progress. Neurochem. Res. 18: 101, 1993.

    Article  PubMed  CAS  Google Scholar 

  5. Kebabian J.W., Calne D.B. Multiple receptors for dopamine. Nature 277: 93, 1979.

    Article  PubMed  CAS  Google Scholar 

  6. Creese I., Sibley D.R., Leff S.E. Agonist interactions with dopamine receptors: focus on radioligand-binding studies. Fed. Proc. 43: 2779, 1984.

    PubMed  CAS  Google Scholar 

  7. Boesgaard S., Hagen C., Andersen A.N., Eldrup E., Lange P. Effect of fenoldopam, a dopamine D-1 receptor agonist, on pituitary, gonadal and thyroid hormone secretion. Clin. Endocrinol. (Oxf.) 30: 231, 1989.

    Article  CAS  Google Scholar 

  8. Hagen C., Andersen A.N., Djursing H. Evidence of altered dopaminergic modulation of Prl, LH, FSH, GH and TSH secretion during chronic partial dopamine receptor blockade in normal women. Acta Endocrinol. (Copenh.) 106: 1, 1984.

    CAS  Google Scholar 

  9. Andersen P.H., Gronvald F.C. Specific binding of 3H-SCH 23390 to dopamine D1 receptors in vivo [published erratum appears in Life Sci 1986, Sep 22; 39 (12): 1117]. Life Sci. 38: 1507, 1986.

    Article  PubMed  CAS  Google Scholar 

  10. Andersen P.H., Nielsen E.B. The dopamine D1 receptor: biochemical and behavioral aspects. Adv. Exp. Med. Biol. 204: 73, 1986.

    Article  PubMed  CAS  Google Scholar 

  11. Monsma F.J. Jr., Mahan L.C., McVittie L.D., Gerfen C.R., Sibley, D.R. Molecular cloning and expression of a D1 dopamine receptor linked to adenylyl cyclase activation. Proc. Natl. Acad. Sci. U.S.A. 87: 6723, 1990.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Sibley D.R., Monsma F.J. Molecular biology of dopamine receptors. Trends Pharmacol. Sci. 13: 61, 1992.

    Article  PubMed  CAS  Google Scholar 

  13. Boesgaard S., Hagen C., Hangaard J., Andersen A.N., Eldrup, E. Effect of dopamine and a dopamine D-1 receptor agonist on pulsatile thyrotrophin secretion in normal women. Clin. Endocrinol. (Oxf.) 32: 423, 1990.

    Article  CAS  Google Scholar 

  14. Denef C., Tilemans D., Andries M. Paracrine control in the anterior pituitary: Growth factors from gonadotrophs control DNA replication in lactotrophs, somatotrophs and corticotrophs. In: Faglia G., Beck-Peccoz P., Ambrosi B., Travaglini P., Spada H., (eds.), Pituitary adenomas: new trends in basic and clinical research. Elsevier Science Publisher BV, 49, 1991 (Abstract).

  15. Nielsen E.B., Andersen P.H. Dopamine receptor occupancy in vivo: behavioral correlates using NNC-112, NNC-687 and NNC-756, new selective dopamine D1 receptor antagonists. Eur. J. Pharmacol. 219: 35, 1992.

    Article  PubMed  CAS  Google Scholar 

  16. Skrumsager B.K., Christensen J.V., Snel S., Seiberling M. Tolerability, safety and pharmacokinetics of single dose and multiple dosing of the selective D1 antagonist NNC 01-0687 in healthy subjects. Psychopharmacology (Berlin) 121: 294, 1995.

    Article  CAS  Google Scholar 

  17. Christensen J.V. Determination of (+)-5-(2,3-dihydrobenzofuran-7-yl) -3-methyl-8-nitro-2,3,4,5-tetrahydro-1H-3-benzazepin-7-ol (NNC 01-0687), a novel dopamine D-1 receptor antagonist, in plasma by solid-phase extraction and high-performance liquid chromatography. J. Chromatogr. 577: 366, 1992.

    Article  PubMed  CAS  Google Scholar 

  18. Fuxe K., Agnati L.F., Anderson K., Eneroth P., Haerfstrand A., Goldstein M. The external layer of the median eminence and the paraventricular hypothalamic nucleus represent two important levels of integration in the neuroendocrine regulation. Studies on peptide-catecholamine interactions give evidence for the existence of “mediasomes”. In: del Pozo E., Flückiger E. (eds.), Dopamine and Neuroendocrine Substances. Academic Press Inc. Ltd., London, 1985, p. 11.

    Google Scholar 

  19. James M.D., MacKenzie F.J., Tuohy Jones P.A., Wilson C.A. Dopaminergic neurones in the zona incerta exert a stimulatory control on gonadotrophin release via D1 dopamine receptors. Neuroendocrinology 45: 348, 1987.

    Article  PubMed  CAS  Google Scholar 

  20. Shupnik M.A., Greenspan S.L., Ridgway E.C. Transcriptional regulation of thyrotropin subunit genes by thyrotropin-releasing hormone and dopamine in pituitary cell culture. J. Biol. Chem. 261: 12675, 1986.

    PubMed  CAS  Google Scholar 

  21. Agner T., Hagen C., Andersen A.N., Djursing H. Increased dopaminergic activity inhibits basal and metoclopramide-stimulated prolactin and thyrotropin secretion. J. Clin. Endocrinol. Metab. 62: 778, 1986.

    Article  PubMed  CAS  Google Scholar 

  22. Delitala G. Dopamine and TSH secretion in man [letter]. Lancet 2: 760, 1977.

    Article  PubMed  CAS  Google Scholar 

  23. Brabant G., Prank K., Hoang Vu C., Hesch R.D., von zur Muhlen A. Hypothalamic regulation of pulsatile thyrotropin secretion. J. Clin. Endocrinol. Metab. 72: 145, 1991.

    Article  PubMed  CAS  Google Scholar 

  24. Kerr D.J., Singh V.K., McConway M.G., Beastall G.H., Connell J.M., Alexander W.D., Davies D.L. Circadian variation of thyrotrophin, determined by ultrasensitive immunoradiometric assay, and the effect of low dose nocturnal dopamine infusion. Clin. Sci. 72: 737, 1987.

    PubMed  CAS  Google Scholar 

  25. Samuels M.H., Henry P., Ridgway E.C. Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion. J. Clin. Endocrinol. Metab. 74: 217, 1992.

    PubMed  CAS  Google Scholar 

  26. Burrow G.N., May P.B., Spaulding S.W., Donabedian R.K. TRH and dopamine interactions affecting pituitary hormones secretion. J. Clin. Endocrinol. Metab. 45: 65, 1977.

    Article  PubMed  CAS  Google Scholar 

  27. Rossmanith W.G., Mortola J.F., Laughlin G.A., Yen S.S. Dopaminergic control of circadian and pulsatile pituitary thyrotropin release in women. J. Clin. Endocrinol. Metab. 67: 560, 1988.

    Article  PubMed  CAS  Google Scholar 

  28. Hagen C., Petersen K., Djursing H., Andersen A.N. Evidence of altered dopaminergic modulation of Prl, LH and TSH secretion in patients with normoprolactinaemic amenorrhoea. Acta Endocrinol. (Copenh.) 106: 8, 1984.

    CAS  Google Scholar 

  29. Martin W.H., Rogol A.D., Kaiser D.L., Thorner M.O. Dopaminergic mechanisms and luteinizing hormone (LH) secretion. II. Differential effects of dopamine and bromocriptine on LH release in normal women. J. Clin. Endocrinol. Metab. 52: 650, 1981.

    Article  PubMed  CAS  Google Scholar 

  30. Halse J., Harris A.G., Kvistborg A., Kjartansson O., Hanssen E., Smiseth O., Djosland O., Hass G., Jervell J. A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects. J. Clin. Endocrinol. Metab. 70: 1254, 1990.

    Article  PubMed  CAS  Google Scholar 

  31. Yamada M., Monden T., Satoh T., Lizuka M., Murakami M., Iriuchijima T., Mori M. Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone in vivo and in vitro (GH3 cells). Biochem. Biophys. Res. Commun. 184: 367, 1992.

    Article  PubMed  CAS  Google Scholar 

  32. Jones K.E., Chin W.W. Differential regulation of thyroid hormone receptor messenger ribonucleic acid levels by thyrotropin-releasing hormone. Endocrinology 128: 1763, 1991.

    Article  PubMed  CAS  Google Scholar 

  33. Philip F., Baxter J.B., Frohman L.A. (eds.). Endocrinology and Metabolism. New York: McGraw-Hill, INC. 1995.

    Google Scholar 

  34. Andersen A.N., Hagen C., Lange P., Boesgaard S., Djursing H., Eldrup E., Micic S. Dopaminergic regulation of gonadotropin levels and pulsatility in normal women. Fertil. Steril. 47: 391, 1987.

    PubMed  CAS  Google Scholar 

  35. Yen S.S., Quigley M.E., Reid R.L., Ropert J.F., Cetel N.S. Neuroendocrinology of opioid peptides and their role in the control of gonadotropin and prolactin secretion. Am. J. Obstet Gynecol. 152: 485, 1985.

    Article  PubMed  CAS  Google Scholar 

  36. Lamberts S.W. The role of somatostatin in the regulation of anterior pituitary hormone secretion and the use of its analogs in the treatment of human pituitary tumors Endocr. Rev. 9: 417, 1988.

    Article  PubMed  CAS  Google Scholar 

  37. Skrumsager B.K., Christensen J.V., Karlson P., Farde L. D1 antagonists: safety, pharmacokinetics and D1 occupancy of NNC 01-0687 in healthy volunteers. American College of Neuropsychopharmacology, 32nd Annual meeting, Po 208: 1993. (Abstract).

  38. Carlson H.E., Ippoliti A.F., Swerdloff R.S. Endocrine effects of acute and chronic cimetidine administration. Dig. Dis. Sci. 26: 428, 1981.

    Article  PubMed  CAS  Google Scholar 

  39. Delitala G., Stubbs W.A., Wass J.A., Jones A., Williams S., Besser G.M. Effects of the H2 receptor antagonist cimetidine on pituitary hormones in man. Clin. Endocrinol. (Oxf.) 11: 161, 1979.

    Article  CAS  Google Scholar 

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Grodum, E., Andersen, M., Hangaard, J. et al. Lack of effect of the dopamine D1 antagonist, NNC 01-0687, on unstimulated and stimulated release of anterior pituitary hormones in males. J Endocrinol Invest 21, 291–297 (1998). https://doi.org/10.1007/BF03350331

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