Histopathological Characteristics of Folliculo-stellate Cells in Pituitary Glands of Wild Type, Obese and High-fat Diet Induced Mice


  • José Filipe Melo Instituto de Anatomia Patológica, Faculdade de Medicina, Universidade de Lisboa
  • Gonçalo Borrecho Center for Interdisciplinary Research Egas Moniz (CiiEM), Monte da Caparinca
  • Noelia Martinez-Sánchez Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
  • Francisco Tortosa Instituto de Anatomia Patológica, Faculdade de Medicina, Universidade de Lisboa; Center for Interdisciplinary Research Egas Moniz (CiiEM), Monte da Caparinca




The anterior pituitary gland regulates growth, metabolism, and reproduction by secreting hormones. Folliculo-stellate cells (FSC) are non-endocrine cells located among hormone-producing cells in the anterior pituitary glands, but little is known about the exact roles of those cells. Although, with their net organization, they seem to have an important role in the hormonal cells regulation and maintenance. In this work, the first ever made in this area, 33 pituitaries of three groups of mice (18 wild type [WT], 11 genetically obese [OB] and 4 under a high fat diet [HFD]) were studied in order to determine if there was any relation between the number of FSC and alterations of the basal metabolism in each group of mice. For that, immunohistochemical staining using the S-100 protein was used and also the Image-J software, to calculate the percentage of FSC present in each sample. The authors found that, although there wasn’t any significant difference between WT and OB mice, the group of HFD mice tend to have substantially higher percentage of FSC than the mice from other groups. This might suggest some yet unknown link between diet, precisely with a high-fat diet, and the presentation of FSC in the anterior pituitary.


Folliculo-stellate cells (FSC), S-100 protein, Basal metabolism, Pituitary


[1] Perez-Castro, C., Renner, U., Haedo, M.R., et al., 2012 Jan. Cellular and molecular specificity of pituitary gland physiology. Physiological Reviews. 92(1), 1-38. DOI: https://doi.org/10.1152/physrev.00003.2011.

[2] Kioussi, C., Carriere, C., Rosenfeld, M.G., 1999 Mar. A model for the development of the hypothalamic– pituitary axis: transcribing the hypophysis. Mechanisms of Development. 81(1-2), 23-35. DOI: https://doi.org/10.1016/s0925-4773(98)00229-9.

[3] Mihai, R., 2014 Oct. Physiology of the pituitary, thyroid, parathyroid and adrenal glands. Surgery (Oxford). 32(10), 504-512. DOI: https://doi.org/10.1016/j.mpsur.2014.07.008.

[4] Yeung, C.M., Chan, C.B., Leung, P.S., et al., 2006 Mar. Cells of the anterior pituitary. International Journal of Biochemistry & Cell Biology. 38(9), 1441- 1449. DOI: https://doi.org/10.1016/j.biocel.2006.02.012.

[5] Amar, A.P., Weiss, M.H., 2003 Jan. Pituitary anatomy and physiology. Neurosurgery Clinics of North America. 14(1), 11-23. DOI: https://doi.org/10.1016/s1042-3680(02)00017-7.

[6] Inoue, K., Couch, E.F., Takano, K., et al., 1999 Aug. The structure and function of folliculo-stellate cells in the anterior pituitary gland. Archives of Histology and Citology. 62(3), 205-218. DOI: https://doi.org/10.1679/aohc.62.205.

[7] Allaerts, W., Vankelecom, H., 2005 Jul. History and perspectives of pituitary folliculo-stellate cell research. European Journal of Endocrinology. 153(1), 1-12. DOI: https://doi.org/10.1530/eje.1.01949.

[8] Perryman, E.K., 1989 Feb. Folliculo-stellate cells of the pituitary gland. Bioscience. 39(2), 81-88. DOI: https://doi.org/10.2307/1310906.

[9] Le Tissier, P.R., Hodson, D.J., Lafont, C., et al., 2012 Aug. Anterior pituitary cell networks. Frontiers in Neuroendocrinology. 33(3), 252-266. DOI: https://doi.org/10.1016/j.yfrne.2012.08.002.

[10] Le Tissier, P.R., Mollard, P., 2021 Nov. Renewing an old interest: Pituitary folliculostellate cells. Journal of Neuroendocrinology. 33(11), e13053. DOI: https://doi.org/10.1111/jne.13053.

[11] Pires, M., Tortosa, F., 2016 Oct. Update on pituitary folliculo-stellate cells. International Archives of Endocrinology Clinical Research. 2, 006. DOI: https://doi.org/10.23937/2572-407X.1510006.

[12] Baes, M., Allaerts, W., Denef, C., 1987 Feb. Evidence for functional communication between folliculo-stellate cells and hormone-secreting cells in perifused anterior pituitary cell aggregates. Endocrinology. 120(2), 685-691. DOI: https://doi.org/10.1210/endo-120-2-685.

[13] Marin, F., Stefaneanu, L., Kovacs, K., 1991 Dec. Folliculostellate cells of the pituitary. Endocrine Pathology. 2(4), 180-192. DOI: https://doi.org/10.1007/BF02915206.

[14] Allaerts, W., Carmeliet, P., Denef, C., 1990 Jun. New perspectives in the function of pituitary folliculo-stellate cells. Molecular and Cellular Endocrinology.71(2), 73-81. DOI: https://doi.org/10.1016/0303-7207(90)90244-3.

[15] Yamashita, M., Qian, Z.R., Sano, T., et al., 2005 May. Immunohistochemical study on so-called follicular cells and folliculostellate cells in the human adenohypophysis. Pathology International. 55(5), 244-247. DOI: https://doi.org/10.1111/j.1440-1827.2005.01820.x.

[16] Stojilkovic, S.S., 2001 Nov. A novel view of the function of pituitary folliculo-stellate cell network. Trends in Endocrinology and Metabolism. 12(9), 378-380.

[17] Horiguchi, K., Yako, H., Yoshida, S., et al., 2016 Oct. S100β-positive cells of mesenchymal origin reside in the anterior lobe of the embryonic pituitary gland. PLoS One. 11(10), e0163981. DOI: https://doi.org/10.1371/journal.pone.0163981.

[18] Elena, P., 2020 Jun. Identification and clinical significance of folliculo-stellate cells in normal hypophysis and adenomas. Moldovan Medical Journal. 63(2), 63-65.

[19] Höfler, H., Walter, G.F., Denk, H., 1984 Mar. Immunohistochemistry of folliculo-stellate cells in normal human adenohypophyses and in pituitary adenomas. Acta Neuropathologica. 65(1), 35-40. DOI: https://doi.org/10.1007/BF00689825.

[20] Girod, C., Trouillas, J., Dubois, M.P., 1985 Sep. Immunocytochemical localization of S-100 protein in stellate cells (folliculo-stellate cells) of the anterior lobe of the normal human pituitary. Cell Tissue Research. 241(3), 505-511. DOI: https://doi.org/10.1007/BF00215885.

[21] Nakajima, T., Yamaguchi, H., Takahashi, K., 1980 Jun. S100 protein in folliculostellate cells of the rat pituitary anterior lobe. Brain Research. 191(2), 523- 531. DOI: https://doi.org/10.1016/0006-8993(80)91300-1.

[22] Cocchia, D., Miani, N., 1980 Dec. Immunocytochemical localization of the brain-specific S-100 protein in the pituitary gland of adult rat. Journal of Neurocytology. 9(6), 771-782. DOI: https://doi.org/10.1007/BF01205018.

[23] Botermann, D.S., Brandes, N., Frommhold, A., et al., 2021 Mar. Hedgehog signaling in endocrine and folliculo-stellate cells of the adult pituitary. Journal of Endocrinology. 248(3), 303-316. DOI: https://doi.org/10.1530/joe-20-0388.

[24] Horiguchi, K., Ilmiawati, C., Fujiwara, K., et al., 2012 Apr. Expression of chemokine CXCL12 and its receptor CXCR4 in folliculostellate (FS) cells of the rat anterior pituitary gland: the CXCL12/CXCR4 axis induces interconnection of FS cells. Endocrinology. 153(4), 1717-1724. DOI: https://doi.org/10.1210/en.2011-1937.

[25] Shirasawa, N., Mabuchi, Y., Sakuma, E., et al., 2004 May. Intercellular communication within the rat anterior pituitary gland: X. Immunohistocytochemistry of S-100 and connexin 43 of folliculo-stellate cells in the rat anterior pituitary gland. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. 278(1), 462-473.

[26] Fauquier, T., Guérineau, N.C., McKinney, R.A., et al., 2001 Jul. Folliculostellate cell network: a route for long-distance communication in the anterior pituitary. Proceedings of the National academy of Sciences of the United States of America. 98(15), 8891- 8896. DOI: https://doi.org/10.1073/pnas.151339598.

[27] Kato, Y., Yoshida, S., Kato, T., 2021 Nov. New insights into the role and origin of pituitary S100β-positive cells. Cell Tissue Research. 386(2), 227-237. DOI: https://doi.org/10.1007/s00441-021-03523-7.

[28] Lloyd, R.V., Mailloux, J., 1988 Nov. Analysis of S-100 protein positive folliculo-stellate cells in rat pituitary tissues. American Journal of Pathology. 133(2), 338.

[29] Horvath, E., Kovacs, K., 2002 Jul. Folliculo-stellate cells of the human pituitary: a type of adult stem cell?. Ultrastructural Pathology. 26(4), 219-228. DOI: https://doi.org/10.1080/01913120290104476.

[30] Inoue, K., Mogi, C., Ogawa, S., et al., 2002 Apr. Are folliculo-stellate cells in the anterior pituitary gland supportive cells or organ-specific stem cells?. Archives of Physiology and Biochemistry. 110(1-2), 50- 53. DOI: https://doi.org/10.1076/apab.

[31] Denef, C., 2008 Jan. Paracrinicity: the story of 30 years of cellular pituitary crosstalk. Journal of Neuroendocrinology. 20(1), 1-70. DOI: https://doi.org/10.1111/j.1365-2826.2007.01616.x.

[32] Devnath, S., Inoue, K., 2008 Jun. An insight to pituitary folliculo-stellate cells. Journal of Neuroendocrinology. 20(6), 687-691. DOI: https://doi.org/10.1111/j.1365-2826.2008.01716.x.

[33] Higuchi, M., Kanno, N., Yoshida, S., et al., 2014 Sep. GFP-expressing S100β-positive cells of the rat anterior pituitary differentiate into hormone-producing cells. Cell Tissue Research. 357(3), 767-779. DOI: https://doi.org/10.1007/s00441-014-1890-0.

[34] Vankelecom, H., Chen, J., 2014 Mar. Pituitary stem cells: where do we stand? Molecular and Cellular Endocrinology. 385(1-2), 2-17. DOI: https://doi.org/10.1016/j.mce.2013.08.018.

[35] Osuna, M., Sonobe, Y., Itakura, E., et al., 2012 Jun. Differentiation capacity of native pituitary folliculostellate cells and brain astrocytes. Journal of Endocrinology. 213(3), 231. DOI: https://doi.org/10.1530/JOE-12-0043.

[36] Fauquier, T., Rizzoti, K., Dattani, M., et al., 2008 Feb. SOX2-expressing progenitor cells generate all of the major cell types in the adult mouse pituitary gland. Proceedings of the National academy of Sciences of the United States of America. 105(8), 2907- 2912. DOI: https://doi.org/10.1073/pnas.0707886105.

[37] Higashi, A.Y., Higashi, T., Furuse, K., et al., 2021 Nov. Claudin-9 constitutes tight junctions of folliculo-stellate cells in the anterior pituitary gland. Scientific Reports. 11(1), 1-14. DOI: https://doi.org/10.1038/s41598-021-01004-z.

[38] Fujiwara, K., Tsukada, T., Horiguchi, K., et al., 2020 Aug. Aldolase C is a novel molecular marker for folliculo-stellate cells in rodent pituitary. Cell Tissue Research. 381(2), 273-284. DOI: https://doi.org/10.1007/s00441-020-03200-1.

[39] Rees, D.A., Lewis, B.M., Lewis, M.D., et al., 2003 Oct. Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK. British Journal of Pharmacology. 140(4), 764. DOI: https://doi.org/10.1038/sj.bjp.0705488.

[40] Vennekens, A., Laporte, E., Hermans, F., et al., 2021 Jun. Interleukin-6 is an activator of pituitary stem cells upon local damage, a competence quenched in the aging gland. Proceedings of the National academy of Sciences of the United States of America. 118(25), e2100052118. DOI: https://doi.org/10.1073/pnas.2100052118.

[41] Vlotides, G., Chen, Y.H., Eigler, T., et al., 2009 Jul. Fibroblast growth factor-2 autofeedback regulation in pituitary folliculostellate TtT/GF cells. Endocrinology. 150(7), 3252-3258. DOI: https://doi.org/10.1210/en.2008-1625.

[42] Morris, J., Christian, H., 2011 May. Folliculo-stellate cells: paracrine communicators in the anterior pituitary. The Open Neuroendocrinology Journal. 4(1), 77-89. DOI: https://doi.org/10.2174/1876528901104010077.

[43] Allaerts, W., Jeucken, P.H., Debets, R., et al., 1997 Jan. Heterogeneity of pituitary folliculo-stellate cells: implications for interleukin-6 production and accessory function in vitro. Journal of Neuroendocrinology. 9(1), 43-53. DOI: https://doi.org/10.1046/j.1365-2826.1997.00555.x.

[44] Laporte, E., Vennekens, A., Vankelecom, H., 2021 Jan. Pituitary remodeling throughout life: Are resident stem cells involved? Frontiers in Endocrinology (Lausanne). 11, 604519. DOI: https://doi.org/10.3389/fendo.2020.604519.

[45] Soji, T., Mabuchi, Y., Kurono, C., et al., 1997 Oct. Folliculo-stellate cells and intercellular communication within the rat anterior pituitary gland. Microscopy Research and Technique. 39(2), 138-149. DOI: https://doi.org/10.1002/ar.a.20040.


How to Cite

Melo, J. F., Borrecho, G., Martinez-Sánchez, N., & Tortosa, F. (2022). Histopathological Characteristics of Folliculo-stellate Cells in Pituitary Glands of Wild Type, Obese and High-fat Diet Induced Mice. Journal of Endocrinology Research, 4(2), 1–9. https://doi.org/10.30564/jer.v4i2.4426


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