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The role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary levels

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Abstract

The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its mRNA in the three levels of the hypothalamo-hypophyseal-ovarian axis was previously demonstrated using immunohistochemistry, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR). In the hypothalamus, PACAP is present in neuroendocrine effector cells and in the median eminence. In the anterior pituitary and ovary, PACAP is transiently present during the proestrous stage of the estrous cycle. In the pituitary, PACAP was observed in gonadotropes. In the ovary, PACAP was demonstrated in the granulosa cells of the preovulatory ovarian follicles. The effect of PACAP on luteinizing hormone (LH) secretion was demonstrated in in vivo and in vitro models. In our work we have studied the role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary levels. At the hypothalamic level, PACAP, administered intracerebroventricularly to female rats before the critical period of the proestrus stage, can inhibit LH release and ovulation. Its inhibiting effect is mediated through corticotropin-releasing factor (CRF) and endogenous opioids. PACAP administered to neonatal female rats delayed the onset of puberty by influencing the luteinizing hormone-releasing hormone (LHRH) neuronal system. In the pituitary gland, the release of PACAP depended on the stage of the estrous cycle and on the time of day the animals were sacrificed. On the day of proestrus, the number of PACAP-releasing cells showed a diurnal change with two peaks (in the morning and in the evening). The peak was much higher in the evening at the end of the LH surge than in the morning.

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References

  • Almeida O. F., Nikolarakis K. E., and Herz A. (1988) Evidence for the involvement of endogenous opioids in the inhibition of luteinizing hormone by corticotropin releasing factor. Endocrinology 122, 1034–1040.

    PubMed  CAS  Google Scholar 

  • Anderson S. T., Sawangjaroen K., and Curlewis J. D. (1996) Pituitary adenylate cyclase activating polypeptide acts within the medial basal hypothalamus to inhibit prolactin and luteinizing hormone secretion. Endocrinology 137, 3424–3429.

    Article  PubMed  CAS  Google Scholar 

  • Arimura A. and Shioda S. (1995) Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Front. Neuroendocrinol. 16, 53–88.

    Article  PubMed  CAS  Google Scholar 

  • Arita J., Kojima Y., and Kimura F. (1993) Measurement of the secretion of a small peptide at the single cell level by the immunoblot assay: thyroidectomy increases the number of substance P-secreting anterior pituitary cells. Endocrinology 132, 2682–2688.

    Article  PubMed  CAS  Google Scholar 

  • Banks W. A., Uchida D., Arimura A., Somogyvári-Vign A., and Shioda S. (1996) Transport of pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier and the prevention of ischemic-induced death of hippocampal neurons. Ann. NY Acad. Sci. 805, 270–277.

    Article  PubMed  CAS  Google Scholar 

  • Choi E. J., Ha C. M., Kim M. S., Kang J. H., Park S. K., Choi W. S., et al. (2000) Central administration of an antisense oligodeoxynucleotide against type I pituitary adenylate cyclase-activating polypeptide receptor suppresses synthetic activities of LHRH-LH axis during the pubertal process. Brain Res. Mol. Brain Res. 80, 35–45.

    Article  PubMed  CAS  Google Scholar 

  • Cristophe J. (1993) Type I receptors for PACAP (a neuropeptide even more important than VIP?) Biochim. Biophys. Acta 1154, 183–199.

    Google Scholar 

  • Culler M. D. and Paschall S. C. (1991) Pituitary adenylate cyclase activating polypeptide (PACAP) potentiates the gonadotropin-releasing activity of luteinizing hormone-releasing hormone. Endocrinology 129, 2260–2262.

    PubMed  CAS  Google Scholar 

  • Dow R. C., Bennie J., and Fink G. (1994) Pituitary adenylate cyclase activating peptide-38 (PACAP-38) is released into hypophyseal portal blood in the normal male and female rat. J. Endocrinol. 142, R1-R4.

    Article  PubMed  CAS  Google Scholar 

  • Gorski R. A. (1986) Sexual differentiation of the brain: model for drug-induced alteration of the reproductive system. Environ. Health Perspect. 70, 163–175.

    Article  PubMed  CAS  Google Scholar 

  • Gottschall P. E., Tatsuno I., Miyata A., and Arimura A. (1990) Characterization and distribution of binding sites for the hypothalamic peptide, pituitary adenylate cyclase activating polypeptide. Endocrinology 127, 272–277.

    PubMed  CAS  Google Scholar 

  • Gräs S., Hannibal J., Georg B., and Fahrenkrug J. (1996) Transient periovulatory expression of pituitary adenylate cyclase activating peptide in rat ovarian cells. Endocrinology 137, 4779–4785.

    Article  PubMed  Google Scholar 

  • Kántor O., Molnár J., Heinzlmann A., Arimura A., Fürst Z., and Köves K. (2000) The inhibitory effect of PACAP38 on ovulation is mediated by CRF and endogenous opioids. Ann. N.Y. Acad. Sci. USA 921, 405–409.

    Article  Google Scholar 

  • Kántor O., Molnár J., Heinzlmann A., Arimura A., Fürst Z., and Köves K. (2001) Study on the hypothalamic factors mediating the inhibitory effect of PACAP38 on ovulation. Peptides 22, 2163–2168.

    Article  PubMed  Google Scholar 

  • Kendall M. E. and Hymer W. C. (1987) Cell blotting: a new approach to quantify hormone secretion from individual rat pituitary cells. Endocrinology 121, 2260–2262.

    PubMed  CAS  Google Scholar 

  • Ko C., In Y. H., and Park-Sarge O. K. (1999) Role of progesterone receptor activation in pituitary adenylate cyclase-activating polypeptide gene expression in rat ovary. Endocrinology 140, 5185–5194.

    Article  PubMed  CAS  Google Scholar 

  • Koenig J. F. R. and Klippel R. A. (1963) The Rat Brain. A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. Williams and Wilkins, Baltimore, MD.

    Google Scholar 

  • Köves K., Arimura A., Görcs T. J., and Somogyvári-Vigh A. (1991) Comparative distribution of immunoreactive pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide in rat forebrain. Neuroendocrinology 54, 159–169.

    Article  PubMed  Google Scholar 

  • Köves K., Arimura A., Vígh S., Somogyvári-Vígh A., and Miller J. (1990) Immunohistochemical demonstration of a novel peptide, pituitary adenylate cyclase activating polypeptide, in the ovine hypothalamus. Endocrinology 127, 264–271.

    PubMed  Google Scholar 

  • Köves K., Kántor O., Scammell J. G., and Arimura A. (1998) PACAP colocalizes with luteinizing and follicle-stimulating hormone immunoreactivities in the anterior lobe of the pituitary gland. Peptides 19, 1069–1072.

    Article  PubMed  Google Scholar 

  • Köves K., Marton J., Molnár J., and Halász B. (1981) (D-Met2, Pro5)-enkephalinamide-induced blockade of ovulation and reversal by naloxone in the rat. Neuroendocrinology 32, 82–86.

    Article  PubMed  Google Scholar 

  • Köves K., Molnár J., Kántor O., Lakatos A., Fógel K., Kausz M., et al. (1998b) Role of PACAP in the regulation of gonadotroph hormone secretion during ontogenesis: a single neonatal injection of PACAP delays puberty and its intracerebroventricular administration before the critical period of proestrous stage blocks ovulation in adulthood. Ann. N.Y. Acad. Sci. USA 865, 590–594.

    Article  Google Scholar 

  • Köves K., Molnár J., Kántor O., Lakatos A., Görcs T. J., Somogyvári-Vígh A., et al. (1996) PACAP participates in the regulation of the hormonal events preceding the ovulation. Acta Biol. Sci. Hung. 47, 239–249.

    Google Scholar 

  • Lee J., Park H. J., Choi H. S., Kwon H. B., Arimura A., Lee B. J., et al. (1999) Gonadotropin stimulation of pituitary adenylate cyclase activating polypeptide (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a follicle survival factor. Endocrinology 140, 18–826.

    Google Scholar 

  • Leonhardt S., Jarry H., Kreipe A., Werstler K., and Wuttke W. (1992) Pituitary adenylate cyclase activating polypeptide (PACAP) stimulates pituitary hormone release in male rats. Neuroendocrinol. Lett. 14, 319–328.

    CAS  Google Scholar 

  • McLusky N., Naftolin F., and Leranth C. (1988) Immunocytochemical evidence for direct synaptic connections between corticotrophin-releasing factor (CRF) and gonadotrophin-releasing hormone (GnRH)-containing neurons in the preoptic area of the rat. Brain Res. 439, 391–395.

    Article  Google Scholar 

  • Merchenthaler I., Kovács G., Lovász G., and Sétáló G. (1980) The preoptico-infundibular LHRH tract of the rat. Brain Res. 1198, 63–75.

    Article  Google Scholar 

  • Miyata A., Arimura A., Dahl D. H., Minamino M., Uehara A., Jiang L., et al. (1989) Isolation of a novel 38 residue hypothalamic peptide which stimulates adenylate cyclase in pituitary cells. Biochem. Biophys. Res. Commun. 164, 567–574.

    Article  PubMed  CAS  Google Scholar 

  • Olcese J., McArdle C. A., Middendorff R., and Greenland K. (1997) Pituitary adenylate cyclase activating polypeptide and vasoactive intestinal peptide receptor expression in immortalized LHRH neurons. J. Neuroendocrinol. 9, 937–943.

    Article  PubMed  CAS  Google Scholar 

  • Osuga Y., Mitsuhashi N., and Mizuno M. (1992) in vivo effect of pituitary adenylate cyclase activating polypeptide 38 (PACAP38) on the secretion of luteinizing hormone (LH) in male rats. Endocrinol. Jpn. 39, 153–156.

    PubMed  CAS  Google Scholar 

  • Palkovits M. (1984) Neuropeptides in the hypothalamohypophyseal system: lateral retrochiasmatic gate for neuronal fibers towards the median eminence. Peptides 5, 35–39.

    Article  PubMed  CAS  Google Scholar 

  • Rawlings S. R. and Hezareh M. (1996) Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP/VIP receptors: actions on the anterior pituitary gland. Endocrinol. Rev. 17, 4–29.

    Article  CAS  Google Scholar 

  • Sawangjaroen K. and Curlewis J. D. (1994) Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) on prolactin, luteinizing hormone and growth hormone secretion in the ewe. J. Neuroendocrinol. 6, 549–555.

    Article  PubMed  CAS  Google Scholar 

  • Shivers B., Görcs T. J., Gottschall P. E., and Arimura A. (1991) Two high-affinity binding sites for pituitary adenylate activating polypeptide. Endocrinology 128, 3055–3065.

    Article  PubMed  CAS  Google Scholar 

  • Szabó E., Nemeskéri Á., Heinzlmann A., Suzuki N., Arimura A., and Köves K. (2002) Cell immunoblot assay demonstrating the release of PACAP from individual anterior pituitary cells of rats and the effect of PACAP on LH release. Regul. Pep. 109, 75–81

    Article  Google Scholar 

  • Tsujii T., Ishizaka K., and Winters S. J. (1994) Effects of pituitary adenylate cyclase-activating polypeptide on gonadotropin secretion and subunit messenger ribonucleic acids in perifused rat pituitary cells. Endocrinology 135, 826–833.

    Article  PubMed  CAS  Google Scholar 

  • Vaudry D., Gonzales B. J., Basille M., Yon L., Fournier A., and Vaudry H. (2000) Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol. Rev. 52, 269–324.

    PubMed  CAS  Google Scholar 

  • Vigh S., Arimura A., Gottschall P. E., Kitada C., Somogyvári-Vigh A., and Childs G. V. (1993) Cytochemical characterization of pituitary target cells for the neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), using biotinylated ligands. Peptides 14, 59–65.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Katalin Köves, Orsolya Kántor, Judith Molnár, Andrea Heinzlmann, Enikö Szabó, Flóra Szabó & Ágnes Nemeskéri

  2. Department of Human Anatomy, Faculty of Medicine, University of Pécs, Pécs, Hungary

    Judit Horváth

  3. U.S.-Japan Biomedical Research Laboratories, Tulane University Hebert Center, Belle Chasse, LA, USA

    Akira Arimura

Authors
  1. Katalin Köves
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  2. Orsolya Kántor
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  3. Judith Molnár
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  4. Andrea Heinzlmann
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  5. Enikö Szabó
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  6. Flóra Szabó
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  7. Ágnes Nemeskéri
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  8. Judit Horváth
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  9. Akira Arimura
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Correspondence to Katalin Köves.

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Köves, K., Kántor, O., Molnár, J. et al. The role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary levels. J Mol Neurosci 20, 141–152 (2003). https://doi.org/10.1385/JMN:20:2:141

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  • DOI: https://doi.org/10.1385/JMN:20:2:141

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