Skip to main content
Log in

In vitro, nitric oxide (NO) stimulates LH secretion and partially prevents the inhibitory effect of dopamine on PRL release

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

Abstract

In recent years nitric oxide (NO) has emerged as an important intra- and intercellular transmitter involved in the control of hypothalamic-pituitary axis. In order to discriminate the potential actions of NO at hypothalamic or pituitary level in the control of PRL and LH release, we have studied PRL and LH secretion by dispersed pituitary cells obtained from males, cycling and lactating females in the presence of 1) sodium nitroprusside (SNP), a NO donor; 2) cyclic guanosine monophosphate (cGMP), the second messenger for a wide range of NO actions; 3) Nw-nitro-L-arginine methyl ester (NAME), a competitive inhibitor of NO synthase (NOS) and 4) oxadialoquinoxalione (OQD) and LY 83,583, antagonists of guanylyl cyclases. We found that SNP (at doses of 100 and 500 μmol) stimulated LH and FSH release and partially blocked the inhibitory action of dopamine (50 and 100 nmol) on prolactin secretion. These effects were not mimicked by cGMP and remained in the presence of OQD and LY 83,583. NAME alone had no significant effect on hormone secretion. These results suggest that NO plays a role in the control of gonadotropins and prolactin secretion acting directly at the pituitary level and that these effects are mediated by mechanisms other than changes in cGMP levels.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Palmer R.M.J., Ashton D.S., Moncada S. Vascular endothelial cells synthesise nitric oxide from L-arginine. Nature 1988, 333: 664–666.

    Article  CAS  PubMed  Google Scholar 

  2. Bredt D.S., Hwang P.M., Snyder S.H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 1990, 347: 768–770.

    Article  CAS  PubMed  Google Scholar 

  3. Bhat G.K., Mahesh V.B., Lamar C.H.A., Ping L., Aguan K., Brann D.W. Histochemical localization of nitric oxide neurons in the hypothalamus: Association with gonadotropin-releasing hormone neurons and colocalization with N-methyl-D-aspartate receptors. Neuroendocrinology 1995, 62: 187–197.

    Article  CAS  PubMed  Google Scholar 

  4. Bredt D.S., Hwang P.M., Glatt C.E., Lowenstein C, Reed R.R., Snyder S.H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 1991, 351: 714–718.

    Article  CAS  PubMed  Google Scholar 

  5. Ceccatelli S, Hulting A.L., Zhang X, Gustafsson L., Villar M., Hökfelt T. Nitric oxide synthase in the rat anterior pituitary gland and the role of nitric oxide in regulation of luteinizing hormone secretion. Proc. Nad. Acad. Sci USA 1993, 90: 11292–11296.

    Article  CAS  Google Scholar 

  6. Moretto M, López F.J., Negro-Vilar A. Nitric oxide regulates luteinizing hormone-releasing hormone secretion. Endocrinology 1993, 133: 2399–2402.

    CAS  PubMed  Google Scholar 

  7. Rettori V., Belova N., Dees W.L., Nyberg C.L., Gimeno M., McCann S.M. Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro. Proc. Natl. Acad. Sci. USA 1993, 90: 10130–10134.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Bonavera J.J.K., Kalra P.S., Kalra S.P. L-arginine/nitric oxide amplifies the magnitude and duration of the luteinizing hormone surge induced by estrogen: Involvement of neuropeptide Y. Endocrinology 1996, 137: 1956–1962.

    CAS  PubMed  Google Scholar 

  9. Bonavera J.J., Sahu A., Kalra P.S., Kalra S.P. Evidence that nitric oxide may mediate the ovarian steroid-induced luteinizing hormone surge: Involvement of excitatory amino acids. Endocrinology 1993, 133: 2482–2487.

    Google Scholar 

  10. Bonavera J.J., Sahu A., Kalra P.S., Kalra S.P. Evidence in support of nitric oxide (NO) involvement in the cyclic release of prolactin and LH surges. Brain Res. 1994, 660: 175–179.

    Article  CAS  PubMed  Google Scholar 

  11. Ping L., Mahesh V.B., Brann D.W. Effect of NMDA and non-NMDA receptor antagonists on pulsatile luteinizing hormone secretion in the adult male rat. Neuroendocrinology 1995, 61: 226–234.

    Article  CAS  PubMed  Google Scholar 

  12. Rettori V., Belova N., Gimeno M., McCann S.M. Inhibition of nitric oxide synthase in the hypothalamus blocks the increase in plasma prolactin induced by intraventricular injection of interleukin-1 alpha in the rat. Neuroimmunomodulation 1994, 1: 116–120.

    Article  CAS  PubMed  Google Scholar 

  13. Pinilla L., González D., Tena-Sempere M., Aguilar R., Aguilar E. Effects of N-methyl-D-aspartate and kainic acid on prolactin secretion in prepubertal female rats. Eur. J. Endocrinol. 1996, 135: 464–468.

    Article  CAS  PubMed  Google Scholar 

  14. Aguilar E, Tena-Sempere M, Aguilar R, González D, Pinilla L. Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion in prepubertal male rats. Eur. J. Endocrinol. 1997, 137: 99–106.

    Article  CAS  PubMed  Google Scholar 

  15. Yu W.H., Walczewska A., Karanth S., McCann S.M. Nitric oxide mediate leptin-induced luteinizing hormone-releasing hormone (LHRH) and LHRH and leptin-induced LH release from the pituitary gland. Endocrinology 1997, 138: 5055–5058.

    Article  CAS  PubMed  Google Scholar 

  16. Tena-Sempere M., Pinilla L., González D., Aguilar E. Involvement of endogenous nitric oxide in the control of pituitary responsiveness to different elicitors of growth hormone release in prepubertal rats. Neuroendocrinology 1996, 64: 146–152.

    Article  CAS  PubMed  Google Scholar 

  17. Kato M. Involvement of nitric oxide in growth hormone (GH)-releasing hormone induced GH secretion in rat pituitary cells. Endocrinology 1992, 131: 2133–2138.

    CAS  PubMed  Google Scholar 

  18. Murad F. The nitric oxide-cyclic GMP signal transduction system for intracellular and intercellular communication. Recent Progr. Horm. Res. 1994, 49: 239–249.

    CAS  PubMed  Google Scholar 

  19. Hoefer M.T., Heiman M.L., Ben-Jonathan N. Prolactin secretion by cultured anterior pituitary cells: Influence of culture conditions and endocrine status of the pituitary donor. Mol. Cell. Endocrinol. 1984, 35: 229–235.

    Article  CAS  PubMed  Google Scholar 

  20. Pinilla L., González D., Tena-Sempere M., Aguilar E. Nitric oxide (NO) stimulates gonadotrophin secretion in vitro through a calcium-dependent, cGMP independent mechanism. Neuroendocrinology 1998, 68: 180–186.

    Article  CAS  PubMed  Google Scholar 

  21. Brunner F., Stessel H., Kukovetz W.R. Novel guanylyl cyclase inhibitor ODQ, reveals role of nitric oxide, but not of cyclic GMP in endothelin-1 secretion. FEBS Lett. 1995, 376: 262–266.

    Article  CAS  PubMed  Google Scholar 

  22. Green I.C., Delaney C.A., Cunningham J.M., Karmiris V., Southern C. Interleukin-1β effects on cyclic GMP and cyclic AMP in cultured rat islets of Langerhans-arginine-dependence and relationships to insulin secretion. Diabetologia 1993, 36: 9–16.

    Article  CAS  PubMed  Google Scholar 

  23. Smith M.A., Vale W.W. Superfusion of rat anterior pituitary cells attached to cytodex beads: validation of a technique. Endocrinology 1980, 107: 1425–1431.

    Article  CAS  PubMed  Google Scholar 

  24. Greenwood F.C., Hunter W.M., Glover J.S. The preparation of 131I-labelled human growth hormone of high specific radioactivity. Biochem. J. 1963, 89: 114–123.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Aguilar E., Tena-Sempere M., González D., Pinilla L. Control of gonadotropin secretion in prepubertal male rats by excitatory amino acids. Andrologia 1996, 28: 163–169.

    Article  CAS  PubMed  Google Scholar 

  26. Duvilanski B.H., Zambruno C., Seilicovich A., Pisera D., Lasaga M., Díaz M.C., Belova N., Rettori V., McCann S.M. Role of nitric oxide in control of prolactin release by the adenohypophysis. Proc. Natl. Acad. Sci. USA 1995, 92: 170–174.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Thorner M.O., Hackett J.T., Murad F., MacLeod R.M. Calcium rather than cyclic AMP as the physiological intracellular regulator of prolactin release. Neuroendocrinology 1980, 31: 390–402.

    Article  CAS  PubMed  Google Scholar 

  28. Tam S.W, Dannies P.S. The role of adenosine 3′,5′-monophosphate in dopaminergic inhibition of prolactin release in anterior pituitary cells. Endocrinology 1981, 109: 403–408.

    Article  CAS  PubMed  Google Scholar 

  29. Schettini G., Cronin M.J., MacLeod R.M. Adenosine 3′,5′-monophosphate (cAMP) and calcium-calmodulin interrelation in the control of prolactin secretion: evidence for dopamine inhibition of cAMP accumulation and prolactin release after calcium mobilization. Endocrinology 1983, 112: 1801–1807.

    Article  CAS  PubMed  Google Scholar 

  30. Delbeke D., Dannies P.S. Stimulation of the adenosine 3′,5′-monophosphate and the Ca2+ messenger systems together reverse dopaminergic inhibition of prolactin release. Endocrinology 1985, 117: 439–446.

    Article  CAS  PubMed  Google Scholar 

  31. Ingram C.D., Bicknell R.J., Mason W.T. Intracellular recordings from bovine anterior pituitary cells: Modulation of spontaneous activity by regulators of prolactin secretion. Endocrinology 1986, 119: 2508–2518.

    Article  CAS  PubMed  Google Scholar 

  32. Koike K., Judd A.M., Login I.S., Yasumoto T., MacLeod R.M. Maitoxin, a calcium channel activator, increases prolactin release from rat pituitary tumor 7315a cells by a mechanism that may involve leukotriene production. Neuroendocrinology 1986, 43: 283–290.

    Article  CAS  PubMed  Google Scholar 

  33. Lafond J., Collu R. Role of calcium and sodium ions in the inhibitory control of baseline and stimulated prolactin release. Endocrinology 1986, 119: 2012–2017.

    Article  CAS  PubMed  Google Scholar 

  34. Martinez de la Escalera G., Weiner R.I. Dissociation of dopamine from its receptor as a signal in the pleiotropic hypothalamic regulation of prolactin secretion. Endocr. Rev. 1992, 13: 241–255.

    CAS  PubMed  Google Scholar 

  35. Conn P.M., Marian J., McMillian M., Stern J., Rogers D., Hamby M., Penna A., Grant E. Gonadotropin-releasing hormone action in the pituitary: a three step mechanism. Endocr. Rev. 1981, 2: 174–185.

    Article  CAS  PubMed  Google Scholar 

  36. Conn P.M., Rogers D.C., Sandhu F.S. Alteration of intracellular calcium levels stimulates gonadotropin release from cultured anterior pituitary cells. Endocrinology 1979, 105: 1122–1127.

    Article  CAS  PubMed  Google Scholar 

  37. Conn P.M., Rogers D.R. Gonadotropin release from pituitary cultures following activation of endogenous ion channels. Endocrinology 1980, 107: 2133–2134.

    Article  CAS  PubMed  Google Scholar 

  38. Conn P.M., Kilpatrick D., Kirshner N. Iontophoretic Ca2+ mobilization in rat gonadotropes and bovine adrenomedullary cells. Cell Calcium 1980, 1: 129–136.

    Article  CAS  Google Scholar 

  39. Laffranchi R., Gogvadze V., Richter C., Spinas G.A. Nitric oxide (nitrogen monoxide, NO) stimulates insulin secretion by inducing calcium release from mitochondria. Biochem. Biophys. Res. Commun. 1994, 217: 584–591.

    Article  Google Scholar 

  40. Willmott N.J., Galione A., Smith P.A. Nitric oxide induces intracellular Ca2+ mobilization and increases secretion of incorporated 5-hydroxytryptamine in rat pancreatic beta-cells. FEBS Lett. 1995, 371: 99–104.

    Article  CAS  PubMed  Google Scholar 

  41. Sortino M.A., Aleppo G., Scapagnini U., Canonico P.L. Involvement of nitric oxide in the regulation of gonadotropin-releasing hormone release from the GT1-1 neuronal cell line. Endocrinology 1994, 134: 1782–1787.

    CAS  PubMed  Google Scholar 

  42. Naor Z., Catt K.J. Independent actions of gonadotropin releasing hormone upon cyclic GMP production and luteinizing hormone release. J. Biol. Chem. 1980, 225: 343–344.

    Google Scholar 

  43. Garhwaite J., Southam E., Boulton C.L., Nielsen E.B., Schmidt K., Mayer B. Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-(1,2,4) oxadiozolo (4,3-a) quinoxalin-1-one. Mol. Pharmacol. 1995, 48: 184–188.

    Google Scholar 

  44. Abou Samra A.B., Catt K.J., Aguilera G. Synthetical atrial natriuretic factors (ANFs) stimulate guanine 3′,5′-monophosphate production but not hormone release in rat pituitary cells: Peptide contamination with a gonadotropin-releasing hormone agonist explains luteinizing hormone-releasing activity of certain ANFs. Endocrinology 1987, 120: 18–24.

    Article  CAS  PubMed  Google Scholar 

  45. McArdle C.A., Poch A., Käppler K. Cyclic guanosine monophosphate production in the pituitary: Stimulation by C-type natriuretic peptide and inhibition by gonadotropin-releasing hormone in aT3-1 cells. Endocrinology 1993, 132: 2065–2072.

    CAS  PubMed  Google Scholar 

  46. Sun P., Kanthasamy A., Yim G.K., Isom G.E. Inhibition of potassium-stimulated dopamine release by the nitric oxide generator isosorbide dinitrate. Neuropharmacology 1995, 34: 205–210.

    Article  CAS  PubMed  Google Scholar 

  47. Childs G.C. (Moriarty), Ellison D., Foster L., Ramaley J.A. Postnatal maturation of gonadotropes in the rat pituitary. Endocrinology 1981, 109: 1683–1692.

    Article  CAS  PubMed  Google Scholar 

  48. Moriarty G.C. Electron microscopic-immunocytochemical studies of rat pituitary gonadotrophs: A sex difference in morphology and cytochemistry of LH cells. Endocrinology 1975, 97: 1215–1225.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

González, D., Aguilar, E. In vitro, nitric oxide (NO) stimulates LH secretion and partially prevents the inhibitory effect of dopamine on PRL release. J Endocrinol Invest 22, 772–780 (1999). https://doi.org/10.1007/BF03343643

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03343643

Key-words

Navigation