Abstract
1. We have previously demonstrated the existence of a dual neuromodulatory regulation of prolactin secretion by the opioid system. In the present work, we evaluated the opioid receptor subtypes involved in both the stimulatory and the inhibitory regulation of prolactin secretion in pregnant rats.
2. Specific opioid agonists and antagonists were administered intracerebro ventricular (i.c.v.) to rats on day 3 and on day 19 pregnancy in rats of pretreated with mifepristone. Blood samples were obtained after decapitation at 12.00 and 18.00 h. Serum prolactin levels were measured by RIA.
3. The μ-selective agonist DAMGO and β-endorphin caused a significant increase in serum prolactin secretion on day 3 of pregnancy, during the diurnal surge and intersurge period. Pretreatment with naloxone prevented the increase on prolactin levels induced by DAMGO. The administration of U-50,488, a κ-selective agonist or DPDPE, a δ-selective agonist, did not modify serum prolactin concentration while the μ1-antagonist naloxonazine reduced significantly serum prolactin levels. On day 19 of pregnancy, the release of prolactin induced by mifepristone was significantly increase by naloxonazine, while the κ-antagonist nor-binaltorfimine induced only a small but significant increase. No effect was observed after administration of the δ-antagonist naltrindole.
4. We conclude that the μ-opioid receptor seems to be more specifically involved in both the stimulatory and inhibitory regulation by the opioid system on prolactin secretion during pregnancy. The increase on serum prolactin levels on day 3 after administration of DAMGO and β-endorphin may suggest the participation of other regulatory mechanisms as the dopaminergic and serotoninergic systems. On day 19, only the endogenous ligands δ did not participate in the regulation of prolactin secretion, while the participation of the κ-opioid receptor was significantly less effective than the endogenous ligand μ. Our results provide evidences of an important role of the opioid system through specific receptors on the regulation of prolactin secretion during early and late pregnancy.
Similar content being viewed by others
REFERENCES
Amenomori, Y., Chen, C. L., and Meites, J. (1970). Serum prolactin levels in rats during different reproductive states. Endocrinology 86: 506-510.
Arbogast, L. A., and Voogt, J. L. (1998). Endogenous opioid peptides contribute to suckling-induced prolactin release by suppressing tyrosine hydroxylase activity and messenger ribonucleic acid levels in tuberoinfundibular dopaminergic neurons. Endocrinology 139: 2857-2862.
Bussman, L. E., and Deis, R. P. (1979). Studies concerning the hormonal induction of lactogenesis by prostaglandin F2α in pregnant rats. J. Steroid Biochem. 11: 1485-1489.
Butcher, R. L., Collins, W. E., and Fugo, N. W. (1974). Plasma concentrations of LH, FSH, prolactin, progesterone and estradiol during the 4 day estrous cycle of the rat. Endocrinology 94: 1704-1708.
Butcher, R. L., Fugo, N. W., and Collins, W. E. (1972). Semicircadian rhythm in plasma levels of PRL during early gestation in the rat. Endocrinology 90: 1195-1197.
Callahan, P., Baumann, M. H., and Rabii, J. (1996). Inhibition of tuberoinfundibular dopaminergic neural activity during suckling: Involvement of μ and κ opiate receptor subtypes. J. Neuroendocrinol. 8: 771-776.
Chen, Y., Mestek, A., Liu, J., Hurley, J. A., and Yu, L. (1993). Molecular cloning and functional expression of a μ-opioid receptor from rat brain. Mol. Pharmacol. 44: 8-12.
Crain, S. M., and Shen, K. F. (1998). Modulation of opioid analgesia, tolerance and dependence by Gs-coupled, GM1 ganglioside-regulated opioid receptor functions. Trends Pharmacol. Sci. 19: 358-365.
Deis, R. P., Carrizo, D. G., and Jahn, G. A. (1989). Suckling-induced prolactin release potentates mifepristone-induced lactogenesis in pregnant rats. J. Reprod. Fertil. 87: 147-153.
Dobson, P. R. M., and Brown, B. L. (1986). Involvement of the hypothalamus in opiate-stimulated prolactin secretion. Regul. Pept. 20: 305-310.
Enjalbert, A., Ruberg, M., Fiore, L., Arancibia, S., Priam, M., and Kordon, C. (1979). Effect of morphine on the dopamine inhibition of pituitary prolactin release in vitro. Eur. J. Pharmacol. 53: 211-212.
Evans, C. J., Keith, D. E., Morrison, H., Magendzo, K., and Edwards, R. H. (1992). Cloning of a delta opioid receptor by functional expression. Science 258: 1952-1955.
Freeman, M. E., Kanyicska, B., Lerant, A., and Nagy, G. (2000). Prolactin: Structure, function and regulation of secretion. Physiol. Rev. 80: 1523-1631.
Hahn, E. F., Carroll-Buatti, M., and Pasternak, G. W. (1981). Irreversible opiate agonists and antagonists: The 14-hydroxyhydromorphine azines. J. Neurosci. 2: 572-576.
Hashimoto, R., and Kimura, F. (1991). Effects of intraventricular injection of delta receptor antagonist ICI154,129 on the secretion of luteinizing hormone and prolactin in proestrous rat. Endocrinol. Jpn. 38: 213-218.
Ieri, T., Chen, H. T., Campbell, G. A., and Meites, J. (1980). Effects of naloxone and morphine on the proestrous surge of prolactin and gonadotropin in the rat. Endocrinology 106: 1568-1570.
Illes, P., and Jackisch, R. (1990). Modulation of catecholamine release in the Central Nervous System by multiple opioid receptors. In Almeida, O. F. X., and Shippenberg, T. S. (eds.), Neurobiology of Opioids, Springer-Verlag, Berlin, pp. 213-225.
Jahn, G. A., Alonso, N., and Deis, R. P. (1986). Ovarian and feto-placental factors and the regulation of prolactin release during pregnancy in the rat. J. Reprod. Fertil. 77: 125-133.
Jahn, G. A., and Deis, R. P. (1987). A possible dual regulation of prolactin release by the serotoninergic system in rats at pro-oestrus and during late pregnancy: Role of ovarian hormones. J. Endocrinol. 112: 367-374.
Jahn, G. A., and Deis, R. P. (1988). Effect of serotonin antagonists on prolactin and progesterone secretion in rats: Evidence that the stimulatory and inhibitory actions of serotonin on prolactin release may be mediated through different receptors. J. Endocrinol. 117: 415-422.
Johnson, N., and Pasternak, G. W. (1984). Binding of 3H-naloxonazine to rat brain membranes. Mol. Pharmacol. 26: 477-483.
Kapoor, R., and Willoughby, J. O. (1990). Activation of opioid receptors in the mediobasal hypothalamus stimulates prolactin secretion in the conscious rats. J. Neuroendocrinol. 2: 347-350.
Kehoe, L., Parman, R., Janik, J., and Callahan, P. (1993). Opiate receptor subtype involvement in the stimulation of prolactin release by β-endorphin in female rats. Neuroendocrinology 57: 875-883.
Krulich, L., Koenig, J. I., Conway, S., McCann, S. M., and Mayfield, M. A. (1986). Opioid κ receptor agonist and the secretion of prolactin (PRL) and growth hormone (GH) in the rat. Neuroendocrinology 42: 75-81.
Leadem, C. A., and Kalra, S. P. (1985). Effects of endogenous opioid peptides and opiate on LH and prolactin secretion and growth hormone secretion in ovariectomized rats. Neuroendocrinology 41: 324-352.
Leadem, C. A., and Yagenova, S. V. (1987). Effects of specific activation of mu, delta and kappa opioid receptors on the secretion of luteinizing hormone and prolactin in the ovariectomized rat. Neuroendocrinology 45: 109-117.
Lee, Y., and Voogt, J. L. (1999). Feedback effects of placental lactogens on prolactin levels and related antigen immunoreactivity of tuberoinfundibular dopaminergic neurons in the arcuate nucleus during pregnancy in the rat. Endocrinolgy 140: 2159-2166.
Loose, M. D., and Kelly, M. J. (1990). Opioids act at μ-receptors to hyperpolarize arcuate neurons via an inwardly rectifying potassium conductance. Brain Res. 513: 15-23.
Manzanares, J., Lookingland, K. J., and Moore, K. E. (1991). Kappa opioid receptor-mediated regulation of dopaminergic neurons in the rat brain. J. Pharmacol. Exp. Ther. 256: 500-505.
Manzanares, J., Wagner, E. J., LaVigne, S. D., Lookingland, K. J., and Moore, K. E. (1992) Sexual differences in kappa opioid receptor-mediated regulation of tuberoinfundibular dopaminergic neurons. Neuroendocrinology 55: 301-307.
Meng, F., Xie, G. X., Thompson, R. C., Mansour, A., Goldstein, A., Watson, S. J., and Akil, H. (1993). Cloning and pharmacological characterisation of a rat kappa opioid receptor. Proc. Natl. Acad. Sci. U.S.A. 90: 9954-9958.
Niswender, G. D., Chen, C. L., Midgley, A. R. Jr., Meites, J., and Ellis, S. (1969). Radioimmunoassay for rat prolactin. Proc. Soc. Exp. Biol. Med. 130: 793-797.
Pasternak, G. W., and Wood, P. L. (1986). Multiple mu receptors. Life Sci. 38: 1889-1898.
Paxinos, G., and Watson, C. (1986). The Rat Brain in Stereotaxic Coordinates, 2nd edn., Academic Press, Sydney.
Sagrillo, C. A., and Voogt, J. L. (1991). Endogenous opioids mediate the nocturnal prolactin surge in the pregnant rat. Endocrinology 129: 925-930.
Selmanoff, M., and Gregerson, K. A. (1986). Suckling-induced prolactin release is suppressed by naloxone and stimulated by β-endorphin. Neuroendocrinology 42: 255-259.
Smith, M. S., and Neill, J. D. (1976). Termination at mid-pregnancy of the two daily surges of plasma prolactin initiated by mating in the rat. Endocrinology 108: 2388-2390.
Snedecor, G. W., and Cochran, W. G. (1967). Statistical Methods, Iowa State University Press, Ames.
Soaje, M., and Deis, R. P. (1994). A modulatory role of endogenous opioids on prolactin secretion at the end of pregnancy in the rat. J. Endocrinol. 140: 97-102.
Soaje, M., and Deis, R. P. (1997). Opiodergic regulation of prolactin secretion during pregnancy: Role of ovarian hormones. J. Endocrinol. 155: 99-106.
Soaje, M., and Deis, R. P. (1999). Participation of the opioid system in the regulation of prolactin secretion in androgenized rats: Effect of ovarian steroids. Eur. J. Pharmacol. 371: 43-49.
Soaje, M., Di Nasso, E., and Deis, R. P. (2002). Regulation by endogenous opioids of suckling-induced prolactin secretion in pregnant and lactating rats: Role of ovarian steroids. J. Endocrinol. 172: 255-261.
Spiegel, K., Kourides, I. A., and Pasternak, G. W. (1982). Prolactin and growth hormone release by morphine in the rat: Different receptor mechanisms. Science 217: 745-749.
Tonkowicz, P. A., Robertson, M., and Voogt, J. L. (1983). Secretion of rat placental lactogen by the fetal placenta and its inhibitory effect on prolactin surges. Biol. Reprod. 28: 707-716.
Wang, L., and Gintzler, A. R. (1995). Morphine tolerance and physical dependence: Reversal of opioid inhibition to enhancement of cyclic AMP formation. J. Neurochem. 64: 1102-1106.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Soaje, M., Deis, R.P. Involvement of Opioid Receptor Subtypes in Both Stimulatory and Inhibitory Effects of the Opioid Peptides on Prolactin Secretion During Pregnancy. Cell Mol Neurobiol 24, 193–204 (2004). https://doi.org/10.1023/B:CEMN.0000018616.00018.98
Issue Date:
DOI: https://doi.org/10.1023/B:CEMN.0000018616.00018.98