Abstract
Prolactinomas are the most common tumor of the human pituitary. They result in excessive prolactin secretion and important changes in the vasculature. Pericytes are perivascular cells associated with capillaries and have crucial roles in physiological and pathological neovascularization. We previously reported that pericytes produce type I and III collagens in the anterior pituitary of adult rats. In addition, pituitary pericytes contained well-developed cell organelles and actively synthesized collagens during early postnatal development. However, the characteristics of pericytes in pituitary tumors are unclear. In this study, we used diethylstilbestrol (DES)-treated rats as an animal model of prolactinoma. Using five common pericyte markers, more pericytes were observed in rats treated with DES for 3 months (prolactinoma) compared to the control. Transmission electron microscopy revealed that attached and semidetached pericytes exhibited active cell organelles. Moreover, we identified pericyte migration between capillaries. Although the fine structure of pituitary pericytes was active in prolactinoma, expressions of type I and III collagen mRNAs were greatly diminished. In sum, the characteristics and functions of pericytes were altered in pituitary tumors. This study is the first to clarify fine structural changes of pericytes in rat prolactinomas and improves our understanding of the function of pericytes under pathological conditions.
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References
Erroi A, Bassetti M, Spada A, Giannattasio G (1986) Microvasculature of human micro-and macroprolactinomas. A morphological study. Neuroendocrinology 43:159–165
Melmed S (2003) Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Invest 112:1603–1618
Baron SH, Sowers JR, Feinberg M (1983) Prolactinoma in a man following industrial exposure to estrogens. West J Med 138:720–722
Gooren LJ, Assies J, Asscheman H, de Slegte R, van Kessel H (1988) Estrogen-induced prolactinoma in a man. J Clin Endocrinol Metab 66:444–446
Spady TJ, McComb RD, Shull JD (1999) Estrogen action in the regulation of cell proliferation, cell survival, and tumorigenesis in the rat anterior pituitary gland. Endocrine 11:217–233
Tachibana M, Lu L, Hiai H, Tamura A, Matsushima Y, Shisa H (2006) Quantitative trait loci determining weight reduction of testes and pituitary by diethylstilbesterol in LEXF and FXLE recombinant inbred strain rats. Exp Anim 55:91–95
Fujiwara K, Davaadash B, Yatabe M, Kikuchi M, Horiguchi K, Kusumoto K, Kouki T, Yashiro T (2008) Reduction of retinaldehyde dehydrogenase 1 expression and production in estrogen-induced prolactinoma of rat. Med Mol Morphol 41:126–131
Mucha SA, Meleń-Mucha G, Godlewski A, Stepień H (2007) Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer 344 rats by the matrix metalloproteinase inhibitor batimastat. Virchows Arch 450:335–341
Elias KA, Weiner RI (1984) Direct arterial vascularization of estrogen-induced prolactin-secreting anterior pituitary tumors. Proc Natl Acad Sci USA 81:4549–4553
Schechter J, Ahmad N, Elias K, Weiner R (1987) Estrogen-induced tumors: changes in the vasculature in two strains of rat. Am J Anat 179:315–323
Schechter J (1972) Ultrastructural changes in the capillary bed of human pituitary tumors. Am J Pathol 67:109–126
van Nesselrooij JH, Hendriksen GJ, Feron VJ, Bosland MC (1992) Pathogenesis of blood-filled cavities in estrogen-induced anterior pituitary tumors in male Sprague-Dawley rats. Toxicol Pathol 20:71–80
Shepro D, Morel NM (1993) Pericyte physiology. FASEB J 7:1031–1038
Fujiwara K, Jindatip D, Kikuchi M, Yashiro T (2010) In situ hybridization reveals that type I and III collagens are produced by pericytes in the anterior pituitary gland of rats. Cell Tissue Res 342:491–495
Horiguchi K, Syaidah R, Fujiwara K, Tsukada T, Ramadhani D, Jindatip D, Kikuchi M, Yashiro T (2013) Expression of small leucine-rich proteoglycans in rat anterior pituitary gland. Cell Tissue Res 351:207–212
Jindatip D, Fujiwara K, Horiguchi K, Tsukada T, Kouki T, Yashiro T (2013) Changes in fine structure of pericytes and novel desmin-immunopositive perivascular cells during postnatal development in rat anterior pituitary gland. Anat Sci Int 88:196–203
Ramadhani D, Tofrizal A, Tsukada T, Yashiro T (2015) Histochemical analysis of laminin α chains in diethylstilbestrol-induced prolactinoma in rats. Acta Histochem Cytochem 48:69–73
Jindatip D, Fujiwara K, Kouki T, Yashiro T (2012) Transmission and scanning electron microscopy study of the characteristics and morphology of pericytes and novel desmin-immunopositive perivascular cells before and after castration in rat anterior pituitary gland. Anat Sci Int 87:165–173
Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15–23
Berger M, Bergers G, Arnold B, Hämmerling GJ, Ganss R (2005) Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization. Blood 105:1094–1101
Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM (2002) Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 160:985–1000
Schlingemann RO, Rietveld FJ, Kwaspen F, van de Kerkhof PC, de Waal RM, Ruiter DJ (1991) Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue. Am J Pathol 138:1335–1347
Ogawa A, Sugihara S, Hasegawa M, Sasaki A, Nakazato Y, Kawada T, Ishiuchi S, Tamura M (1990) Intermediate filament expression in pituitary adenomas. Virchows Arch B Cell Pathol Incl Mol Pathol 58:341–349
Díaz-Flores L, Gutiérrez R, Madrid JF, Varela H, Valladares F, Acosta E, Martín-Vasallo P, Díaz-Flores L Jr (2009) Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 24:909–969
Pfister F, Feng Y, vom Hagen F, Hoffmann S, Molema G, Hillebrands JL, Shani M, Deutsch U, Hammes HP (2008) Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes 57:2495–2502
Dore-Duffy P, Owen C, Balabanov R, Murphy S, Beaumont T, Rafols JA (2000) Pericyte migration from the vascular wall in response to traumatic brain injury. Microvasc Res 60:55–69
Lindahl P, Johansson BR, Levéen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245
Hellström M, Gerhardt H, Kalén M, Li X, Eriksson U, Wolburg H, Betsholtz C (2001) Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153:543–553
Horiguchi K, Kikuchi M, Kusumoto K, Fujiwara K, Kouki T, Kawanishi K, Yashiro T (2010) Living-cell imaging of transgenic rat anterior pituitary cells in primary culture reveals novel characteristics of folliculo-stellate cells. J Endocrinol 204:115–123
Horiguchi K, Fujiwara K, Ilmiawati C, Kikuchi M, Tsukada T, Kouki T, Yashiro T (2011) Caveolin 3-mediated integrin b1 signaling is required for the proliferation of folliculostellate cells in rat anterior pituitary gland under the influence of extracellular matrix. J Endocrinol 210:29–36
Ilmiawati C, Horiguchi K, Fujiwara K, Yashiro T (2012) Matrix metalloproteinase-9 expression in folliculostellate cells of rat anterior pituitary gland. J Endocrinol 212:363–370
Acknowledgements
We are grateful to Megumi Yatabe and Dr. Dini Ramadhani (Jichi Medical University, School of Medicine, Japan) for their suggestions regarding the prolactinoma rat model. We also thank David Kipler of Supernatant Communications for revising the language of the manuscript. This work was supported by grants as follows; Dr. Depicha Jindatip was supported by the Ratchadaphiseksomphot Endowment Fund Part of the Research Grant for New Scholar CU Researcher’s Project Grant Number RGN_2558_015_07_30, Dr. Ken Fujiwara was supported by JSPS KAKENHI Grant Number 17K08517, Dr. Apiwat Mutirangura was supported by the Thailand Research Fund Grant Number DPG5980005, and Dr. Takashi Yashiro was supported by promotional funds for the Keirin Race of the Japan Keirin Association.
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Jindatip, D., Fujiwara, K., Sarachana, T. et al. Characteristics of pericytes in diethylstilbestrol (DES)-induced pituitary prolactinoma in rats. Med Mol Morphol 51, 147–155 (2018). https://doi.org/10.1007/s00795-018-0180-4
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DOI: https://doi.org/10.1007/s00795-018-0180-4