Interactions Between Two Different G Protein-Coupled Receptors in Reproductive Hormone-Producing Cells: The Role of PACAP and Its Receptor PAC1R

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Sep 30

PMID 27681724

Citations 6

Authors

Haruhiko Kanasaki

Aki Oride

Tomomi Hara

Tselmeg Mijiddorj

Unurjargal Sukhbaatar

Satoru Kyo

Affiliations

Soon will be listed here.

Abstract

Gonadotropin-releasing hormone (GnRH) and gonadotropins are indispensable hormones for maintaining female reproductive functions. In a similar manner to other endocrine hormones, GnRH and gonadotropins are controlled by their principle regulators. Although it has been previously established that GnRH regulates the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)-both gonadotropins-from pituitary gonadotrophs, it has recently become clear that hypothalamic GnRH is under the control of hypothalamic kisspeptin. Prolactin, which is also known as luteotropic hormone and is released from pituitary lactotrophs, stimulates milk production in mammals. Prolactin is also regulated by hypothalamic factors, and it is thought that prolactin synthesis and release are principally under inhibitory control by dopamine through the dopamine D2 receptor. In addition, although it remains unknown whether it is a physiological regulator, thyrotropin-releasing hormone (TRH) is a strong secretagogue for prolactin. Thus, GnRH, LH and FSH, and prolactin are mainly regulated by hypothalamic kisspeptin, GnRH, and TRH, respectively. However, the synthesis and release of these hormones is also modulated by other neuropeptides in the hypothalamus. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hypothalamic peptide that was first isolated from sheep hypothalamic extracts based on its ability to stimulate cAMP production in anterior pituitary cells. PACAP acts on GnRH neurons and pituitary gonadotrophs and lactotrophs, resulting in the modulation of their hormone producing/secreting functions. Furthermore, the presence of the PACAP type 1 receptor (PAC1R) has been demonstrated in these cells. We have examined how PACAP and PAC1R affect GnRH- and pituitary hormone-secreting cells and interact with their principle regulators. In this review, we describe our understanding of the role of PACAP and PAC1R in the regulation of GnRH neurons, gonadotrophs, and lactotrophs, which are regulated mainly by kisspeptin, GnRH, and TRH, respectively.

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References

Kanasaki H, Oride A, Kyo S . Role of pituitary adenylate cyclase-activating polypeptide in modulating hypothalamus-pituitary neuroendocrine functions in mouse cell models. J Neuroendocrinol. 2014; 27(1):1-7. DOI: 10.1111/jne.12230. View

Kanasaki H, Mijiddorj T, Sukhbaatar U, Oride A, Miyazaki K . Pituitary adenylate cyclase-activating polypeptide (PACAP) increases expression of the gonadotropin-releasing hormone (GnRH) receptor in GnRH-producing GT1-7 cells overexpressing PACAP type I receptor. Gen Comp Endocrinol. 2013; 193:95-102. DOI: 10.1016/j.ygcen.2013.07.013. View

Purwana I, Kanasaki H, Oride A, Mijiddorj T, Shintani N, Hashimoto H . GnRH-induced PACAP and PAC1 receptor expression in pituitary gonadotrophs: a possible role in the regulation of gonadotropin subunit gene expression. Peptides. 2010; 31(9):1748-55. DOI: 10.1016/j.peptides.2010.05.012. View

Harris D, Bonfil D, Chuderland D, Kraus S, Seger R, Naor Z . Activation of MAPK cascades by GnRH: ERK and Jun N-terminal kinase are involved in basal and GnRH-stimulated activity of the glycoprotein hormone LHbeta-subunit promoter. Endocrinology. 2002; 143(3):1018-25. DOI: 10.1210/endo.143.3.8675. View

Hashimoto H, Nogi H, Mori K, Ohishi H, Shigemoto R, Yamamoto K . Distribution of the mRNA for a pituitary adenylate cyclase-activating polypeptide receptor in the rat brain: an in situ hybridization study. J Comp Neurol. 1996; 371(4):567-77. DOI: 10.1002/(SICI)1096-9861(19960805)371:4<567::AID-CNE6>3.0.CO;2-2. View

Purwana I, Kanasaki H, Mijiddorj T, Oride A, Miyazaki K . Induction of dual-specificity phosphatase 1 (DUSP1) by pulsatile gonadotropin-releasing hormone stimulation: role for gonadotropin subunit expression in mouse pituitary LbetaT2 cells. Biol Reprod. 2011; 84(5):996-1004. DOI: 10.1095/biolreprod.110.088526. View

Messager S, Chatzidaki E, Ma D, Hendrick A, Zahn D, Dixon J . Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005; 102(5):1761-6. PMC: 545088. DOI: 10.1073/pnas.0409330102. View

Li S, Grinevich V, Fournier A, Pelletier G . 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. 1996; 41(1-2):157-62. DOI: 10.1016/0169-328x(96)00086-1. View

Yonehara T, Kanasaki H, Yamamoto H, Fukunaga K, Miyazaki K, Miyamoto E . Involvement of mitogen-activated protein kinase in cyclic adenosine 3',5'-monophosphate-induced hormone gene expression in rat pituitary GH(3) cells. Endocrinology. 2001; 142(7):2811-9. DOI: 10.1210/endo.142.7.8226. View

10.

Gershengorn M . Mechanism of thyrotropin releasing hormone stimulation of pituitary hormone secretion. Annu Rev Physiol. 1986; 48:515-26. DOI: 10.1146/annurev.ph.48.030186.002503. View

11.

Kanasaki H, Fukunaga K, Takahashi K, Miyazaki K, Miyamoto E . Mitogen-activated protein kinase activation by stimulation with thyrotropin-releasing hormone in rat pituitary GH3 cells. Biol Reprod. 1999; 61(1):319-25. DOI: 10.1095/biolreprod61.1.319. View

12.

Kimura S, Ohshige Y, Lin L, Okumura T, Yanaihara C, Yanaihara N . Localization of pituitary adenylate cyclase-activating polypeptide (PACAP) in the hypothalamus-pituitary system in rats: light and electron microscopic immunocytochemical studies. J Neuroendocrinol. 1994; 6(5):503-7. DOI: 10.1111/j.1365-2826.1994.tb00612.x. View

13.

Koves K, Kantor O, Scammell J, Arimura A . PACAP colocalizes with luteinizing and follicle-stimulating hormone immunoreactivities in the anterior lobe of the pituitary gland. Peptides. 1998; 19(6):1069-72. DOI: 10.1016/s0196-9781(98)00049-7. View

14.

Purwana I, Kanasaki H, Oride A, Mijiddorj T, Miyazaki K . Expression of the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) potentiates the effects of GnRH on gonadotropin subunit gene expression. Biochem Biophys Res Commun. 2011; 410(2):295-300. DOI: 10.1016/j.bbrc.2011.05.135. View

15.

Jin L, Tsumanuma I, Ruebel K, Bayliss J, Lloyd R . Analysis of homogeneous populations of anterior pituitary folliculostellate cells by laser capture microdissection and reverse transcription-polymerase chain reaction. Endocrinology. 2001; 142(5):1703-9. DOI: 10.1210/endo.142.5.8117. View

16.

Ormandy C, Camus A, Barra J, Damotte D, Lucas B, Buteau H . Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev. 1997; 11(2):167-78. DOI: 10.1101/gad.11.2.167. View

17.

Seminara S, Messager S, Chatzidaki E, Thresher R, Acierno Jr J, Shagoury J . The GPR54 gene as a regulator of puberty. N Engl J Med. 2003; 349(17):1614-27. DOI: 10.1056/NEJMoa035322. View

18.

Novaira H, Ng Y, Wolfe A, Radovick S . Kisspeptin increases GnRH mRNA expression and secretion in GnRH secreting neuronal cell lines. Mol Cell Endocrinol. 2009; 311(1-2):126-34. PMC: 3534746. DOI: 10.1016/j.mce.2009.06.011. View

19.

Castellano J, Navarro V, Fernandez-Fernandez R, Castano J, Malagon M, Aguilar E . Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat. Mol Cell Endocrinol. 2006; 257-258:75-83. DOI: 10.1016/j.mce.2006.07.002. View

20.

Anderson S, Sawangjaroen K, Curlewis J . Pituitary adenylate cyclase-activating polypeptide acts within the medial basal hypothalamus to inhibit prolactin and luteinizing hormone secretion. Endocrinology. 1996; 137(8):3424-9. DOI: 10.1210/endo.137.8.8754770. View