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Advent and Recent Advances in Research on the Role of Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) in the Regulation of Gonadotropic Hormone Secretion of Female Rats

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Abstract

PACAP (ADCYAP1) was isolated from ovine hypothalami. PACAP activates three distinct receptor types: G-protein coupled PAC1, VPAC1, and VPAC2 with seven transmembrane domains. Eight splice variants of PAC1 receptor are described. A part of the hypothalamic PACAP is released into the hypophyseal portal circulation. Both hypothalamic and pituitary PACAP are involved in the dynamic control of gonadotropic hormone secretion. In female rats, PACAP in the paraventricular nucleus is upregulated in the morning and pituitary PACAP is upregulated in the late evening of the proestrus stage of the reproductive cycle. PACAP mRNA peak in the hypothalamic PVN precedes the LHRH release into the portal circulation. It is supposed that PACAP peak is evoked by the elevated estrogen on proestrous morning. At the beginning of the so-called critical period of the same day, PACAP level starts to decline allowing LHRH release into the portal circulation, resulting in the LH surge that evokes ovulation. Just before the critical period, icv-administered exogenous PACAP blocks the LH surge and ovulation. The blocking effect of PACAP is mediated through CRF and endogenous opioids. The effect of the pituitary-born PACAP depends on the intracellular cross-talk between PACAP and LHRH.

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Abbreviations

ABC:

Avidin-biotin-peroxidase complex

AC:

Adenylyl cyclase

ADCYAP:

Adenylate cyclase-activating polypeptide

ACTH:

Adrenocorticotropic hormone

ARC:

Arcuate nucleus

Biot-PACAP38:

Biotinylated PACAP38

BBB:

Blood-brain barrier

CIBA:

Cell immunoblot assay

CRH:

Corticotropic hormone-releasing hormone

FG:

Fluorogold

FS:

Folliculostellate cells

FSH:

Follicle-stimulating hormone

GH:

Growth hormone

HPLC:

High-pressure liquid chromatography

ia:

Intraarterial

icv:

Intracerebroventricular

ip:

Intraperitoneal

iv:

Intravenous

LH:

Luteinizing hormone

LHRH:

Luteinizing hormone-releasing hormone

MBH:

Medial basal hypothalamus

ME:

Median eminence

α-MSH:

Melanocyte-stimulating hormone

ODN:

Antisense oligodeoxynucleotide

PACAP:

Pituitary adenylate cyclase-activating polypeptide

PKC:

Protein kinase-C

PLC:

Phospholipase-C

PRL:

Prolactin

PVN:

Paraventricular nucleus

RIA:

Radioimmunoassay

S-EIA:

Sandwich enzyme immunoassay

SON:

Supraoptic nucleus

TGF:

Transforming growth factor

TSH:

Thyrotropin-releasing hormone

VIP:

Vasoactive intestinal polypeptide

References

  • Arimura A, Somogyvári-Vígh A, Miyata A et al (1991) Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. Endocrinology 129:2787–2789

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Arya V, Demarco VG, Issar M, Hochhaus G (2006) Contrary to adult, neonatal rats show pronounced brain uptake of corticosteroids. Drug Metab Dispos 34:939–942

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Barr GD, Barraclough CA (1978) Temporal changes in medial basal hypothalamic LH-RH correlated with plasma LH during the rat estrous cycle and following electrochemical stimulation of the medial preoptic area in pentobarbital treated proestrous rats. Brain Res 148:413–423

    PubMed  CAS  Google Scholar 

  • Basille M, Vaudry D, Coulouarn Y et al (2000) Comparative distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites and PACAP receptor mRNAs in the rat brain during development. J Comp Neurol 425:495–509

    PubMed  CAS  Google Scholar 

  • Blechman J, and Levkowitz G (2013) Alternative splicing of the pituitary adenylate cyclase-activating polypeptide receptor PAC1: mechanisms of fine tuning of brain activity. Frontiers in Endocrinology 4, Article 55.

  • Borzsei R, Mark L, Tamas A et al (2009) Presence of pituitary adenylate cyclase activating polypeptide-38 in human plasma and milk. Eur J Endocrinol 160:561–565

    PubMed  CAS  Google Scholar 

  • Butcher RL, Collins WE, Fugo NW (1974) Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrous cycle of the rat. Endocrinology 94:1704–1708

    PubMed  CAS  Google Scholar 

  • Butt AM, Jones HC, Abbott NJ (1990) Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study. J Physiology 429:47–62

    CAS  Google Scholar 

  • Choi EJ, Ha CM, Kim MS 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

    PubMed  CAS  Google Scholar 

  • Cimini V, Van Noorden S, Mahadeva H, Polak JM (1994) The cell blot assay in analysis of rat anterior pituitary cell secretion. Histochem J 6:59–66

    Google Scholar 

  • Cornford EM, Braun LD, Oldendorf WH (1982) Developmental modulations of blood-brain barrier permeability as an indicator of changing nutritional requirements in the brain. Pediatr Res 16:324–328

    PubMed  CAS  Google Scholar 

  • Counis R, Laverrière JN, Garrel-Lazayres G et al (2007) What is the role of PACAP in gonadotrope function? Peptides 28:1797–1804

    PubMed  CAS  Google Scholar 

  • Cristophe J (1993) Type 1 receptors for PACAP (a neuropeptide even more important than VIP?) Biochim. Biophys Acta 1154:183–199

    Google Scholar 

  • Culler MD, Paschall CS (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 

  • Dejda A, Bourgault S, Doan ND et al (2011) Identification by photoaffinity labeling of the extracellular N-terminal domain of PAC1 receptor as the major binding site for PACAP. Biochimie 93:669–677

    PubMed  CAS  Google Scholar 

  • Dore R, Iemolo A, Smith KL, Wang X, Cottone P, Sabino V (2013) CRF mediates the anxiogenic and anti-rewarding, but not the anorectic effects of PACAP. Neuropsychopharmacology 38:2160–2169

    PubMed Central  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Dürr K, Norsted E, Gömüç B, Suarez E, Hannibal J, Meister B (2007) Presence of pituitary adenylate cyclase-activating polypeptide (PACAP) defines a subpopulation of hypothalamic POMC neurons. Brain Res 1186:203–211

    PubMed  Google Scholar 

  • Everett JW, Sawyer CH (1949) A neural timing factor in the mechanism by which progesterone advances ovulation in the cyclic rat. Endocrinology 45:581–595

    PubMed  CAS  Google Scholar 

  • Everett JW, Sawyer CH (1950) A 24-hour periodicity in the “LH-release” apparatus of female rats disclosed by barbiturate sedation. Endocrinology 47:198–218

    PubMed  CAS  Google Scholar 

  • Fahrenkrug J, Steenstrup BR, Hannibal J, Alm P, Ottesen B (1996) Role of PACAP in the female reproductive organs. Ann NY Acad Sci 805:394–407

    PubMed  CAS  Google Scholar 

  • Fujii Y, Okada Y, Moore JP Jr, Dalkin AC, Winters SJ (2002) Evidence that PACAP and GnRH down-regulate follicle-stimulating hormone-beta mRNA levels by stimulating follistatin gene expression: effects on folliculostellate cells, gonadotrophs and LbetaT2 gonadotroph cells. Mol Cell Endocrinol 192:55–64

    PubMed  CAS  Google Scholar 

  • Gathei MA, Takahashi K, Suzuki Y, Gardiner J, Jones PM, Bloom SR (1993) Distribution, molecular characterization of pituitary adenylate cyclase-activating polypeptide and its precursor encoding messenger RNA in human and rat tissue. J Endocrinol 136:159–166

    Google Scholar 

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

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gottschall PE, Tatsuno I, Miyata A, 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 

  • Gottschall PE, Tatsuno I, Arimura A (1991) Hypothalamic binding sites for pituitary adenylate cyclase activating polypeptide: characterization and molecular identification. FASEB J 5:194–199

    PubMed  CAS  Google Scholar 

  • Grafer CM, Halvorson LM (2013) Androgen receptor drives transcription of rat PACAP in gonadotrope cells. Mol Endocrinol 27:1343–1356

    PubMed Central  PubMed  CAS  Google Scholar 

  • Grafer CM, Thomas R, Lambrakos L, Montoya I, White S, Halvorson LM (2009) GnRH stimulates expression of PACAP in the pituitary gonadotropes via both the PKA and PKC signaling systems. Mol Endocrinol 23:1022–1032

    PubMed Central  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Gras S, Hedetoft C, Pedersen SH, Fahrenkrug J (2000) Pituitary adenylate cyclase-activating peptide stimulates acute progesterone production in rat granulosa/lutein cells via two receptor subtypes. Biol Reprod 63:206–212

    PubMed  CAS  Google Scholar 

  • Gras S, Host E, Fahrenkrug J (2005) Role of pituitary adenylate cyclase-activating peptide (PACAP) in the cyclic recruitment of immature follicles in the rat ovary. Regul Pept 128:69–74

    PubMed  Google Scholar 

  • Gray SR, Cummings KJ, Jirik FR, Sherwood NM (2001) Targeted disruption of the pituitary adenylate cyclase-activating polypeptide gene results in early postnatal death associated with dysfunction of lipid and carbohydrate metabolism. Mol Endocrinol 15:1739–1747

    PubMed  CAS  Google Scholar 

  • Grinevich V, Fournier A, Pelletier G (2002) Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on corticotropin-releasing hormone (CRH) gene expression in the rat hypothalamic paraventricular nucleus. Peptides 23:2197–2202

    Google Scholar 

  • Ha CM, Kang JH, Choi EJ et al (2000) Progesterone increases mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP) and type I PACAP receptor (PAC(1)) in the rat hypothalamus. Brain Res Mol Brain Res 78:59–68

    PubMed  CAS  Google Scholar 

  • Halvorson LM (2013) PACAP modulates GnRH signaling in gonadotropes. Mol. Cell Endocrinol. doi:10.1016/j.mce

  • Hannibal J (2002) Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study. J Comp Neurol 453:389–417

    PubMed  CAS  Google Scholar 

  • Hannibal J, Mikkelsen JD, Fahrenkrug J, Larsen PJ (1995) Pituitary adenylate cyclase-activating peptide gene expression in corticotropin-releasing factor-containing parvicellular neurons of the rat hypothalamic paraventricular nucleus is induced by colchicine, but not by adrenalectomy, acute osmotic, ether, or restraint stress. Endocrinology 136:116–124

    Google Scholar 

  • Harada T, Kanasaki H, Mutiara S, Oride A, Miyazaki K (2007) Cyclic adenosine 3′,5′-monophosphate/protein kinase A and mitogen-activated protein kinase 3/1 pathways are involved in adenylate cyclase-activating polypeptide 1-induced common α-glycoprotein subunit gene (Cga) expression in mouse pituitary gonadotroph LβT2 cells. Biol Reprod 77:707–716

    PubMed  CAS  Google Scholar 

  • Harmar AJ, Arimura A, Gozes I et al (1998) International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev 50:265–270

    PubMed  CAS  Google Scholar 

  • Harmar AJ, Fahrenkrug J, Gozes I et al (2012) Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 166:4–17

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hart GR, Gowing H, Burrin JM (1992) Effects of a novel hypothalamic peptide pituitary adenylate cyclase-activating polypeptide, on pituitary hormone release in rats. J Endocrinol 134:33–41

    PubMed  CAS  Google Scholar 

  • Hashimoto H, Ishihara T, Shigemoto R, Mori K, Nagata S (1993) Molecular cloning and tissue distribution of a receptor for pituitary adenylate cyclase-activating polypeptide. Neuron 11:333–342

    PubMed  CAS  Google Scholar 

  • Hashimoto H, Nogi H, Mori K et al (1996) Distribution of mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study. J Comp Neurol 371:567–577

    PubMed  CAS  Google Scholar 

  • Heinzlmann A, Kirilly E, Meltzer K et al (2008) PACAP is transiently expressed in anterior pituitary gland of rats. In situ hybridization and cell immunoblot assay studies. Peptides 29:571–577

    PubMed  CAS  Google Scholar 

  • Helyes Z, Pozsgai G, Börzsei R et al (2007) Inhibitory effect of PACAP-38 on acute neurogenic and non-neurogenic inflammatory processes in the rat. Peptides 28:1847–1855

    PubMed  CAS  Google Scholar 

  • Hosoya M, Onda H, Ogi K et al (1993) Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP). Biochem Biophys Res Commun 194:133–143

    PubMed  CAS  Google Scholar 

  • Hulting A-L, Lindgren JA, Hokfelt T et al (1985) Leukotriene C4 as a mediator of luteinizing hormone release from rat anterior pituitary cells. Proc Natl Acad Sci U S A 82:3834–3838

    PubMed Central  PubMed  CAS  Google Scholar 

  • Isaac ER, Sherwood NM (2008) Pituitary adenylate cyclase-activating polypeptide (PACAP) is important for embryo implantation in mice. Mol Cell Endocrinol 280:13–19

    PubMed  CAS  Google Scholar 

  • Jakab B, Reglodi D, Józsa R, Hollósy T, Tamás A, Lubics A, Lengvári I, Oroszi G, Szilvássy Z, Szolcsányi J, Németh J (2004) Distribution of PACAP-38 in the central nervous system of various species determined by a novel radioimmunoassay. J Biochem Biophys Methods 61:189–198

    PubMed  CAS  Google Scholar 

  • Jamen F, Rodriguez-Henche N, Pralong F et al (2000a) PAC1 null females display decreased fertility. Ann NY Acad Sci 921:400–404

    PubMed  CAS  Google Scholar 

  • Jamen F, Persson K, Bertrand G et al (2000b) PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance. J Clin Invest 105:1307–1315

    PubMed Central  PubMed  CAS  Google Scholar 

  • ** L, Tsumanuma I, Ruebel KH, Bayliss JM, Lloyd RV (2001) Analysis of homogenous population of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription-polymerase chain reaction. Endocrinology 142:1703–1709

    PubMed  CAS  Google Scholar 

  • Journot L, Waeber C, Pantaloni C et al (1995) Differential signal transduction by six splice variants of the pituitary adenylate cyclase-activating peptide (PACAP) receptor. Biochem Soc Trans 23:133–137

    PubMed  CAS  Google Scholar 

  • Kanasaki H, Mutiara S, Oride A, Purwana IN, Miyazaki K (2009) Pulse frequency-dependent gonadotropin gene expression by adenylate cyclase activating polypeptide 1 in perifused mouse pituitary gonadotroph LbetaT2 cells. Biol Reprod 81:465–472

    PubMed  CAS  Google Scholar 

  • Kanasaki H, Purwana IN, Oride A, Mijiddorj T, Sukhbaatar U, Miyazaki K (2013a) Circulating kisspeptin and pituitary adenylate cyclase-activating polypeptide (PACAP) do not correlate with gonadotropin serum levels. Gynecol Endocrinol 29:583–587

    PubMed  CAS  Google Scholar 

  • Kanasaki H, Purwana IN, Miyazaki K (2013b) Possible role of PACAP and its PAC1 receptor in the differential regulation of pituitary LHbeta- and FSHbeta-subunit gene expression by pulsatile GnRH stimulation. Biol Repro 88(35):1–5

    Google Scholar 

  • Kántor O, Molnár J, Arimura A, Köves K (2000a) PACAP38 and PACAP27 administered intracerebroventricularly have an opposite effect on LH secretion. Peptides 21:817–820

    Google Scholar 

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

    Google Scholar 

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

    PubMed  Google Scholar 

  • Kivipelto L, Absood A, Arimura A, Sundler F, Håkanson R, Panula P (1992) The distribution of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity is distinct from helodermin- and helospectin-like immunoreactivities in the rat brain. J Chem Neuroanat 5:85–94

    PubMed  CAS  Google Scholar 

  • Koh PO, Kwak SD, Kim HJ, Roh G, Kim JH, Kang SS, Choi WS, Cho GJ (2003) Expression patterns of pituitary adenylate cyclase activating polypeptide and its type I receptor mRNAs in the rat placenta. Mol Reprod Dev 64(1):27–31

    PubMed  CAS  Google Scholar 

  • Koh PO, Won CK, Noh HS, Cho GJ, Choi WS (2005) Expression of pituitary adenylate cyclase activating polypeptide and its type I receptor mRNAs in human placenta. J Vet Sci 6:1–5

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Köves K, Molnár J, Kántor O, Görcs T, Arimura A (1996a) New aspects of the neuroendocrine role of PACAP. Ann NY Acad Sci 805:648–654

    PubMed  Google Scholar 

  • Köves K, Molnár J, Kántor O et al (1996b) PACAP participates in the regulation of the hormonal events preceding the ovulation. Acta Biol Hung 47:239–249

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Köves K, Molnár J, Kántor O et al (1998b) Role of PACAP in the regulation of gonadotroph hormone secretion during ontogenesis: a single neonatal injection of PACAP delays the puberty, icv administration in adulthood is able to block the ovulation. Ann NY Acad Sci 865:590–594

    PubMed  Google Scholar 

  • Köves K, Vereczki V, Kausz M et al (2002) PACAP and VIP in the photoneuroendocrine system (PNES). Med Sci Mon 8:SR5–SR20

    Google Scholar 

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

    PubMed  Google Scholar 

  • Larivière S, Garrel G, Robin MT, Counis R, Cohen-Tannoudji J (2006) Differential mechanisms for PACAP and GnRH cAMP induction contribute to cross-talk between both hormones in the gonadotrope LbetaT2 cell line. Ann NY Acad Sci 1070:376–379

    PubMed  Google Scholar 

  • Lariviere S, Garrel G, Simon V et al (2007) Gonadotropin-releasing hormone couples to 3′,5′-cyclicadenosine-5’-monophosphate pathway through novel protein kinase Cδ and -ε in LβT2 gonadotrope cells. Endocrinology 148:1099–2107

    PubMed  CAS  Google Scholar 

  • Lariviere S, Garrel-Lazayres G, Simon V et al (2008) Gonadotropin-releasing hormone inhibits pituitary adenylyl cyclase-activating polypeptide coupling to 3′,5′-Cyclic adenosine-5′-monophosphate pathway in LβT2 gonadotrope cells through novel protein kinase C isoforms and phosphorylation of pituitary adenylyl cyclase-activating polypeptide type I receptor. Endocrinology 149:6389–6398

    PubMed  CAS  Google Scholar 

  • Leong SK, Ling EA (1990) Labelling neurons with fluorescent dyes administered via intravenous, subcutaneus or intraperitoneal route. J Neurosci Methods 32:15–23

    PubMed  CAS  Google Scholar 

  • Li S, Grinevich V, Fournier A, Pelletier G (1996) Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the rat brain. Brain Res Mol Brain Res 41:157–162

    PubMed  CAS  Google Scholar 

  • Mahesh VB (1985) The dynamic interaction between steroids and gonadotropins in the mammalian ovulatory cycle. Neurosci Biobehav Rev 9:245–260

    PubMed  CAS  Google Scholar 

  • Mahesh VB, Brann DW (1998) Regulation of the preovulatory gonadotropin surge by endogenous steroids. Steroids 63:616–629

    PubMed  CAS  Google Scholar 

  • Masuo Y, Ohtaki T, Masuda Y, Tsuda M, Fu**o M (1992) Binding sites for pituitary adenylate cyclase activating polypeptide (PACAP): comparison with vasoactive intestinal polypeptide (VIP) binding site localization in rat brain sections. Brain Res 575:113–123

    PubMed  CAS  Google Scholar 

  • Masuo Y, Tokito F, Matsumoto Y, Shimamoto N, Fu**o M (1994) Ontogeny of pituitary adenylate cyclase-activating polypeptide (PACAP) and its binding sites in the rat brain. Neurosci Lett 170:43–46

    PubMed  CAS  Google Scholar 

  • Mikkelsen JD, Hannibal J, Fahrenkrug J, Larsen PJ, Olcese J, McArdle C (1995) Pituitary adenylate cyclase activating peptide-38 (PACAP-38), PACAP-27, and PACAP related peptide (PRP) in the rat median eminence and pituitary. J Neuroendocrinol 7:47–55

    PubMed  CAS  Google Scholar 

  • Miyata A, Arimura A, Dahl RR et al (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 184:567–574

    Google Scholar 

  • Miyata A, Jiang L, Dahl RD et al (1990) Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem Biophys Res Commun 170:643–648

    PubMed  CAS  Google Scholar 

  • Moore JP Jr, Winters SJ (2008) Weaning and the developmental changes in follicle-stimulating hormone, pituitary adenylate cyclase-activating polypeptide, and inhibin B in the male rat. Biol Reprod 78:752–760

    PubMed Central  PubMed  CAS  Google Scholar 

  • Moore JP Jr, Burger LL, Dalkin AC, Winters SJ (2005) Pituitary adenylate cyclase activating polypeptide messenger RNA in the paraventricular nucleus and anterior pituitary during the rat estrous cycle. Biol Reprod 73:491–499

    PubMed  CAS  Google Scholar 

  • Moore JP Jr, Villafuerte BC, Unick CA, Winters SJ (2009) Developmental changes in pituitary adenylate cyclase activating polypeptide expression during the perinatal period: possible role in fetal gonadotroph regulation. Endocrinology 150:4802–4809

    PubMed Central  PubMed  CAS  Google Scholar 

  • Moore JP Jr, Yang RQ, Winters SJ (2012) Targeted pituitary overexpression of pituitaryadenylate-cyclase activating polypeptide alters postnatal sexual maturation in male mice. Endocrinology 153:1421–1434

    PubMed Central  PubMed  CAS  Google Scholar 

  • Morrow JA, Lutz EM, West KM, Fink G, Harmar AJ (1993) Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP). FEBS Lett 329:99–105

    PubMed  CAS  Google Scholar 

  • Mounien L, Bizet P, Boutelet I, Gourcerol G, Fournier A, Vaudry H, Jégou S (2006) Pituitary adenylate cyclase-activating polypeptide directly modulates the activity of proopiomelanocortin neurons in the rat arcuate nucleus. Neuroscience 43:155–163

    Google Scholar 

  • Németh J, Tamás A, Józsa R, Horváth J, Jakab B, Lengvári I, Arimura A, Lubics A, Reglődi D (2006) Changes in PACAP levels in the central nervous system after ovariectomy and castration. Ann NY Acad Sci 1070:468–473

    PubMed  Google Scholar 

  • Ohtaki T, Masuda Y, Ishibashi Y, Kitada C, Arimura A, Fu**o M (1993) Purification and characterization of the receptor for pituitary adenylate cyclase-activating polypeptide. J Biol Chem 268:26650–26657

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ortmann O, Asmus W, Diedrich K, Schulz K-D, Emons G (1999) Interactions of ovarian steroids with pituitary adenylate cyclase-activating polypeptide and GnRH in anterior pituitary cells. Eur J Endocrinol 140:207–214

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Academic, San Diego, 2005

    Google Scholar 

  • Radleff-Schlimme A, Leonhardt S, Wuttke W, Jarry H (1998) Evidence for PACAP to be an autocrine factor on gonadotrope cells. Ann NY Acad Sci 865:486–491

    PubMed  CAS  Google Scholar 

  • Rawlings SR, Hezareh M (1996) Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP/vasoactive intestinal polypeptide receptors: actions on the anterior pituitary gland. Endocr Rev 17:4–29

    PubMed  CAS  Google Scholar 

  • Rawlings SR, Piuz I, Schlegel W, Bockaert J, Journot I (1995) Differential expression of pituitary adenylate cyclase activating polypeptide/vasoactive intestinal polypeptide receptor subtypes in clonal pituitary somatotrophs and gonadotrophs. Endocrinology 136:2088–2098

    PubMed  CAS  Google Scholar 

  • Reglodi D, Gyarmati J, Ertl T et al (2010) Alterations of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in the human plasma during pregnancy and after birth. J Endocrinol Invest 33:443–445

    PubMed  CAS  Google Scholar 

  • Reglodi D, Tamas A, Koppan M, Szogyi D, and Welke L (2012) Role of PACAP in female fertility and reproduction at gonadal level—recent advances. Frontiers in Endocrinology, article 155

  • Resch JM, Boisvert JP, Hourigan AE, Mueller CR, Yi SS, Choi S (2011) Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate cyclase-activating polypeptide induces hypophagia and thermogenesis. Am J Physiol Regul Integr Comp Physiol 301:R1625–R1634

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sawangjaroen K, Curlewis JD (1994) Effects 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

    PubMed  CAS  Google Scholar 

  • Scaldaferri ML, Modesti A, Palumbo C et al (2000) Pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-receptor type 1 expression in rat and human placenta. Endocrinology 141:1158–1167

    PubMed  CAS  Google Scholar 

  • Sherwood NM, Adams BA, Isaac ER, Wu S, Fradinger EA (2007) Knocked down and out: PACAP in development, reproduction and feeding. Peptides 28:1680–1687

    PubMed  CAS  Google Scholar 

  • Shintani N, Mori W, Hashimoto H et al (2002) Defects in reproductive functions in PACAP-deficient female mice. Regul Pept 109:45–48

    PubMed  CAS  Google Scholar 

  • Shivers BD, Görcs TJ, Gottschall PE, Arimura A (1991) Two high affinity binding sites for pituitary adenylate cyclase-activating polypeptide have different tissue distributions. Endocrinology 128:3055–3065

    PubMed  CAS  Google Scholar 

  • Skoglösa Y, Takei N, Lindholm D (1999) Distribution of pituitary adenylate cyclase activating polypeptide mRNA in the develo** rat brain. Brain Res Mol Brain Res 65:1–13

    PubMed  Google Scholar 

  • Spengler D, Waeber C, Pantaloni C et al (1993) Differential signal transduction by five splice variants of the PACAP receptor. Nature 365:170–175

    PubMed  CAS  Google Scholar 

  • Suzuki N, Harada M, Kitada C et al (1993) Production of immunoreactive pituitary adenylate cyclase activating polypeptide (PACAP) by human neuroblastoma cells, IMR-32: detection and characterization with monoclonal and polyclonal antibodies against different epitopes of PACAP. J Biochem 13:49–56

    Google Scholar 

  • Szabó E, Nemeskéri Á, Heinzlmann A, Suzuki N, Arimura A, Köves K (2002a) Cell immunoblot assay study 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

    Google Scholar 

  • Szabó F, Horváth J, Heinzlmann A, Arimura A, Köves K (2002b) Neonatal PACAP administration in rats delays puberty through the influence of the LHRH neuronal system. Regul Pep 109:49–55

    Google Scholar 

  • Szabó E, Nemeskéri Á, Arimura A, Köves K (2004) Effect of PACAP on LH release, studied by cell immunoblot assay, depends on the gender, on the time of day and in female rats on the day of estrous cycle. Regul Pep 123:139–145

    Google Scholar 

  • Tachibana T, Saito ES, Takahashi H, Saito S, Tomonaga S, Boswell T (2004) Anorexigenic effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide in the chick brain are mediated by corticotrophin-releasing factor. Regul Pept 120:99–105

    PubMed  CAS  Google Scholar 

  • Takata F, Dohgu S, Yamauchi A et al (2013) In vitro blood-brain barrier models using brain capillary endothelial cells isolated from neonatal and adult rats retain age-related barrier properties. PLoS One 8:e55166

    PubMed Central  PubMed  CAS  Google Scholar 

  • Tamada Y, Tanaka M, Ichitani Y, Okamura H, Yanaihara N, Ibata Y (1994) Pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactive neuronal elements in rat hypothalamus and median eminence with special reference to morphological background of its effect on anterior pituitary—light and electron microscopic immunocytochemistry. Neurosci Lett 180:105–108

    PubMed  CAS  Google Scholar 

  • Tsujii T, Winters SJ (1995) Effects of pulsatile pituitary adenylate cyclase activating polypeptide (PACAP) on gonadotropin secretion and subunit mRNA levels in perifused rat pituitary cells. Life Sci 56:1103–1111

    PubMed  CAS  Google Scholar 

  • Tsujii T, Ishizaka K, Winters SJ (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

    PubMed  CAS  Google Scholar 

  • Uchida D, Arimura A, Somogyvári-Vigh A, Shioda S, Banks WA (1996) Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide. Brain Res 736:280–286

    PubMed  CAS  Google Scholar 

  • Vereczki V, Köves K, Tóth ZS et al (2003) Pituitary adenylate cyclase-activating polypeptide does not colocalize with vasoactive intestinal polypeptide in the hypothalamic magnocellular nuclei and posterior pituitary of cats and rats. Endocrine 22:225–237

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Weiss B, Davidkova G, Zhou LW (1999) Antisense RNA gene therapy for studying and modulating biological processes. Cell Mol Life Sci 55:334–358

    PubMed  CAS  Google Scholar 

  • Winters SJ, Moore JP Jr (2011) PACAP, an autocrine/paracrine regulator of gonadotrophs. Biol Reprod 84:844–850

    PubMed Central  PubMed  CAS  Google Scholar 

  • Winters SJ, Ghooray D, Fujii Y, Moore JP Jr, Nevitt JR, Kakar SS (2007) Transcriptional regulation of follistatin expression by GnRH in mouse gonadotroph cell lines: evidence for a role for cAMP signaling. Mol Cell Endocrinol 271:45–54

    PubMed  CAS  Google Scholar 

  • Zheng W, Grafer CM, Halvorson LM (2014) Interaction of gonadal steroids and gonadotropin-releasing hormone on pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP receptor expression in cultured rat anterior pituitary cells. Reprod Sci 21:41–51

    PubMed  Google Scholar 

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Acknowledgments

We are very grateful to Anna Takáts for her excellent technical assistance. This work was supported by the Department of Human Morphology and Developmental Biology, Semmelweis University, Budapest, Hungary.

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Authors and Affiliations

  1. Department of Human Morphology and Developmental Biology, Faculty of Medicine, Semmelweis University, Tűzoltó u. 58, H-1094, Budapest, Hungary

    Katalin Köves & Andrea Heinzlmann

  2. Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Orsolya Kántor

  3. Department of Clinical Veterinary Medicine and Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, UK

    András Lakatos

  4. Department of Conservative Dentistry and Endodontics, Faculty of Dentistry, Semmelweis University, Budapest, Hungary

    Enikő Szabó

  5. Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary

    Eszter Kirilly

  6. Cincinnati Children’s Hospital Medical Center, Cincinnati, USA

    Flóra Szabó

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  1. Katalin Köves
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  2. Orsolya Kántor
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  3. András Lakatos
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  7. Flóra Szabó
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Correspondence to Katalin Köves.

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Köves, K., Kántor, O., Lakatos, A. et al. Advent and Recent Advances in Research on the Role of Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) in the Regulation of Gonadotropic Hormone Secretion of Female Rats. J Mol Neurosci 54, 494–511 (2014). https://doi.org/10.1007/s12031-014-0294-7

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