Faculty Profiles - AIZAWA Sayaka

Papers - AIZAWA Sayaka

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Ghrelin increases intracellular Ca²⁺ concentration in the various hormone-producing cell types of the rat pituitary gland. Reviewed International journal

Mami Yamazaki, Sayaka Aizawa, Toru Tanaka, Takafumi Sakai, Ichiro Sakata

Neuroscience letters 526 ( 1 ) 29 - 32 2012.9

Language：English Publishing type：Research paper (scientific journal)

Ghrelin, isolated from the stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), has potent growth hormone release ability in vivo and in vitro. Although GHS-R is abundantly expressed in the pituitary gland, there is no direct evidence of a relationship between hormone-producing cells and functional GHS-R in the pituitary gland. The aim of this study was to determine which anterior pituitary cells respond to ghrelin stimulation in male rats. We performed Fura-2 Ca(2+) imaging analysis using isolated pituitary cells, and performed immunocytochemistry to identify the type of pituitary hormone-producing cells. In Fura-2 Ca(2+) imaging analysis, ghrelin administration increased the intracellular Ca(2+) concentration in approximately 50% of total isolated anterior pituitary cells, and 20% of these cells strongly responded to ghrelin. Immunocytochemical analysis revealed that 82.9 ± 1.3% of cells that responded to ghrelin stimulation were GH-immunopositive. On the other hand, PRL-, LH-, and ACTH-immunopositive cells constituted 2.0 ± 0.3%, 12.6 ± 0.3%, and 2.5 ± 0.8% of ghrelin-responding pituitary cells, respectively. TSH-immunopositive cells did not respond to ghrelin treatment. These results suggest that ghrelin directly acts not only on somatotrophs, but also on mammotrophs, gonadotrophs, and corticotrophs in the rat pituitary gland.

DOI： 10.1016/j.neulet.2012.07.063

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Molecular identification of GHS-R and GPR38 in Suncus murinus. Reviewed International journal

Airi Suzuki, Yuko Ishida, Sayaka Aizawa, Ichiro Sakata, Chihiro Tsutsui, Anupom Mondal, Koike Kanako, Takafumi Sakai

Peptides 36 ( 1 ) 29 - 38 2012.7

Language：English Publishing type：Research paper (scientific journal)

We previously identified ghrelin and motilin genes in Suncus murinus (suncus), and also revealed that motilin induces phase III-like strong contractions in the suncus stomach in vivo, as observed in humans and dogs. Moreover, repeated migrating motor complexes were found in the gastrointestinal tract of suncus at regular 120-min intervals. We therefore proposed suncus as a small laboratory animal model for the study of gastrointestinal motility. In the present study, we identified growth hormone secretagogue receptor (GHS-R) and motilin receptor (GPR38) genes in the suncus. We also examined their tissue distribution throughout the body. The amino acids of suncus GHS-R and GPR38 showed high homology with those of other mammals and shared 42% amino acid identity. RT-PCR showed that both the receptors were expressed in the hypothalamus, medulla oblongata, pituitary gland and the nodose ganglion in the central nervous system. In addition, GHS-R mRNA expressions were detected throughout the stomach and intestine, whereas GPR38 was expressed in the gastric muscle layer, lower intestine, lungs, heart, and pituitary gland. These results suggest that ghrelin and motilin affect gut motility and energy metabolism via specific receptors expressed in the gastrointestinal tract and/or in the central nervous system of suncus.

DOI： 10.1016/j.peptides.2012.04.019

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Detailed analysis of the δ-crystallin mRNA-expressing region in early development of the chick pituitary gland. Reviewed International journal

Makiko Inoue, Tomoya Shiina, Sayaka Aizawa, Ichiro Sakata, Hiroyasu Takagi, Takafumi Sakai

Journal of molecular histology 43 ( 3 ) 273 - 80 2012.6

Language：English Publishing type：Research paper (scientific journal)

Although δ-crystallin (δ-crys), also known as lens protein, is transiently expressed in Rathke's pouch (RP) of the chick embryo, detailed temporal and spatial expression patterns have been obscure. In this study, to understand the relationship between the δ-crys mRNA-expressing region and RP formation, we examined the embryonic expression pattern of δ-crys mRNA in the primordium of the adenohypophysis. δ-crys mRNA expression was initially found at stage 15 anterior to the foregut and posterior to the invaginated oral ectoderm. After RP formation, the δ-crys mRNA was expressed in the post-ventral region of RP and the anterior region of RP. δ-crys mRNA expression was then restricted to the cephalic lobe of the pituitary gland. From stage 20, the δ-crys and alpha-glycoprotein subunit (αGSU) mRNA-expressing regions were almost completely overlapping. The αGSU mRNA-expressing region is thought to be the primordium of the pars tuberalis, and these regions were overlapped with the Lhx3 mRNA-expressing region. The intensity of δ-crys mRNA expression gradually decreased with development and completely disappeared by stage 34. These results suggest that the embryonic chick pituitary gland consists of two different regions labeled with δ-crys and Lhx3.

DOI： 10.1007/s10735-012-9407-1

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Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus. Reviewed International journal

Anupom Mondal, Zuoyun Xie, Yuki Miyano, Chihiro Tsutsui, Ichiro Sakata, Yoichi Kawamoto, Sayaka Aizawa, Toru Tanaka, Sen-ichi Oda, Takafumi Sakai

American journal of physiology. Gastrointestinal and liver physiology 302 ( 10 ) G1207-15 2012.5

Language：English Publishing type：Research paper (scientific journal)

Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.

DOI： 10.1152/ajpgi.00379.2011

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Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis. Reviewed International journal

Sayaka Aizawa, Takafumi Sakai, Ichiro Sakata

The Journal of endocrinology 212 ( 3 ) 383 - 94 2012.3

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Thyroid-stimulating hormone (TSH)-producing cells of the pars tuberalis (PT) display distinct characteristics that differ from those of the pars distalis (PD). The mRNA expression of TSHβ and αGSU in PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism for TSHβ expression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on laser-captured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of the KA2, which is an ionotropic glutamic acid receptor (iGluR). In addition, the amino acid transporter A2 (ATA2), also known as the glutamine transporter, and glutaminase (GLS), as well as GLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid on TSHβ expression and αGSU expression in PT slice cultures. l-Glutamine and l-glutamic acid significantly stimulated TSHβ expression in PT slices after 2- and 4-h treatments, and the effect of l-glutamic acid was stronger than that of l-glutamine. In contrast, treatment with glutamine and glutamic acid did not affect αGSU expression in the PT or the expression of TSHβ or αGSU in the PD. These results strongly suggest that glutamine is taken up by PT cells through ATA2 and that glutamic acid locally converted from glutamine by Gls induces TSHβ expression via the KA2 in an autocrine and/or paracrine manner in the PT.

DOI： 10.1530/JOE-11-0388

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Expression of a thyroglobulin (Tg) variant in mouse kidney glomerulus Reviewed

Huhehasi Wu, Sayuri Suzuki, Donald F. Sellitti, Sonia Q. Doi, Kazunari Tanigawa, Sayaka Aizawa, Takeshi Akama, Akira Kawashima, Masayo Mishima, Norihisa Ishii, Akio Yoshida, Ichiro Hisatome, Nancy L. Koles, Ryohei Katoh, Koichi Suzuki

Biochemical and Biophysical Research Communications 389 ( 2 ) 269 - 273 2009.11

マウス腎臓におけるサイログロブリン遺伝子断片の発現と意義

Wu Huhehasi, 鈴木さゆり, Sellitti Donald, Doi Sonia, 赤間剛, 相沢清香, 川島晃, 谷川和也, 吉田明雄, 加藤良平, 鈴木幸一

日本内分泌学会雑誌 85 ( 2 ) 784 - 785 2009.9

腎メサンジウム細胞に発現するサイログロブリン遺伝子産物のクローニング甲状腺自己免疫と糸球体腎炎とのリンク

Wu Huhehasi, 赤間剛, 相沢清香, 川島晃, 谷川和也, 吉田明雄, 鈴木幸一

日本内分泌学会雑誌 84 ( 1 ) 210 - 210 2008.4

Diurnal Change of Thyroid-Stimulating Hormone mRNA Expression in the Rat Pars Tuberalis Reviewed

S. Aizawa, S. Hoshino, I. Sakata, A. Adachi, S. Yashima, A. Hattori, T. Sakai

Journal of Neuroendocrinology 19 ( 11 ) 839 - 846 2007.11

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