Skip to main content

Advertisement

SpringerLink
Log in

Ultrastructural immunolocalization of IGF-1 and insulin receptors in rat pituitary culture: evidence of a functional interaction between gonadotroph and lactotroph cells

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

We have investigated the expression of receptors for insulin and insulin-like growth factor 1 (IGF-1) in rat pituitary cells in vitro and examined the morphological and proliferative changes induced in adenohypophyseal cells by insulin and IGF-1. The proliferation of lactotrophs was determined by double-immunostaining for bromodeoxyuridine and prolactin. Incubation with insulin (10, 100 or 1000 ng/ml) or IGF-1 (5, 30 or 100 ng/ml) for 48 or 72 h significantly increased the number of lactotrophs undergoing mitosis. Co-incubation of insulin or IGF-1 with genistein (25 μM), an inhibitor of the tyrosine kinase receptor, reduced the proliferation of lactotrophs elicited by the hormone and the growth factor. The receptors for insulin and IGF-1 were localized in intact pituitary cells by ultrastructural immunocytochemistry with the colloidal gold-protein A technique. Gonadotrophs expressed both receptors, specific labelling being restricted to this cell type. Electron-microscopical observations of pituitary cell cultures incubated with insulin or IGF-1 revealed gonadotroph cells exhibiting the fine-structural features of enhanced protein synthetic activity. These findings suggest that both insulin and IGF-1 are able to induce the proliferation of lactotrophs through an indirect mechanism mediated by a factor synthesized by gonadotroph cells, in addition to stimulating the biosynthetic activity of the gonadotroph in a direct manner.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Adashi EY, Hsueh AJ, Yen SS (1981) Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinology 108:1441–1449

    PubMed  CAS  Google Scholar 

  • Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M, Fukami Y (1987) Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 262:5592–5595

    PubMed  CAS  Google Scholar 

  • Albert PR (2002) G protein preferences for dopamine D2 inhibition of prolactin secretion and DNA synthesis in GH4 pituitary cells. Mol Endocrinol 16:1903–1911

    Article  PubMed  CAS  Google Scholar 

  • Arita J, Hashi A, Hoshi K, Mazawa S, Suzuki S (1998) D2 dopamine-receptor mediated inhibition of proliferation of rat lactotropes in culture is accompanied by changes in cell shape. Neuroendocrinology 68:163–171

    Article  PubMed  CAS  Google Scholar 

  • Atkin SL, Landolt AM, Jeffreys RV, Hipkin L, Radcliffe J, Squire CR, White MC (1993) Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas. J Clin Endocrinol Metab 77:1059–1066

    Article  PubMed  CAS  Google Scholar 

  • Bach MA, Bondy CA (1992) Anatomy of the pituitary insulin-like growth factor system. Endocrinology 131:2588–2594

    Article  PubMed  CAS  Google Scholar 

  • Childs GV, Armstrong J (2001) Sites of epidermal growth factor synthesis and action in the pituitary: paracrine and autocrine interactions. Clin Exp Pharmacol Physiol 28:249–252

    Article  PubMed  CAS  Google Scholar 

  • De Keyser J, Wilczak N, De Backer JP, Herroelen L, Vauquelin G (1994) Insulin-like growth factor-I receptors in human brain and pituitary gland: an autoradiographic study. Synapse 17:196–202

    Article  PubMed  Google Scholar 

  • De Paul AL, Pons P, Aoki A, Torres A (1997) Different behaviour of lactotrophs cells in response to angiotensin II and thyrotropin-releasing hormone. Cell Mol Neurobiol 17:245–258

    Article  PubMed  Google Scholar 

  • De Paul AL, Bonaterra M, Aoki A, Torres AI (2000) Cellular and functional interactions between gonadotrophs and lactotrophs in pituitary cell cultures. Med Electron Microsc 33:231–240

    Article  PubMed  Google Scholar 

  • Dykstra MJ (1993) A manual of applied techniques for biological electron microscopy. Plenum, New York

    Google Scholar 

  • Fernández M, Sanchez Franco F, Palacios N, Sánchez I, Villuendas G, Cacicedo L (2003) Involvement of VIP on IGF-1-induced proliferation of rat pituitary lactotrophs in primare culture: evidence for an autocrine and/or paracrine regulatory system. Neuroendocrinology 77:341–352

    Article  PubMed  CAS  Google Scholar 

  • Foti M, Moukil MA, Dudognon P, Carpentier JL (2004) Insulin and IGF-1 receptor trafficking and signalling. Novartis Found Symp 262:125–147

    PubMed  CAS  Google Scholar 

  • Fruchtman S, McVey DC, Borski RJ (2002) Characterization of pituitary IGF-I receptors: modulation of prolactin and growth hormone. Am J Physiol Regul Integr Comp Physiol 283:R468–R476

    PubMed  CAS  Google Scholar 

  • Goodyer CG, De Stephano L, Lai WH, Guyda HJ, Posner BI (1984) Characterization of insulin-like growth factor receptors in rat anterior pituitary, hypothalamus, and brain. Endocrinology 114:1187–1195

    PubMed  CAS  Google Scholar 

  • Gutiérrez S, Petiti JP, De Paul AL, Mukdsi JH, Aoki A, Torres AI, Orgnero EM (2005) Antagonic effects of oestradiol in interaction with IGF-1 on proliferation of lactotroph cells in vitro. Histochem Cell Biol 124:291–301

    Article  PubMed  CAS  Google Scholar 

  • Honda J, Oomizu S, Kiuchi Y, Komatsu N, Takeuchi S, Takahashi S (2000) Identification of epidermal growth factor mRNA-expressing cells in the mouse anterior pituitary. Neuroendocrinology 71:155–162

    Article  PubMed  CAS  Google Scholar 

  • Houslay MD, Wakelam MJO (1988) Structure and function of the receptor for insulin. In: Cooke BA, King RJB, Van Der Molen HJ (eds) Hormones and their actions, part II. Elsevier, Amsterdam, pp 321–348

    Google Scholar 

  • Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34

    Article  PubMed  CAS  Google Scholar 

  • Kanematsu T, Irahara M, Miyake T, Shitsukawa K, Aono T (1991) Effect of insulin-like growth factor I on gonadotropin release from the hypothalamus-pituitary axis in vitro. Acta Endocrinol 125:227–233

    PubMed  CAS  Google Scholar 

  • LeRoith D, Bondy C, Yakar S, Liu JL, Butler A (2001) The somatomedin hypothesis. Endocr Rev 22:53–74

    Article  CAS  Google Scholar 

  • Maldonado C, Aoki A (1986) Improvement of prolactin immuno-labeling in osmium-fixed acrylic-embedded pituitary gland. Basic Appl Histochem 30:301–305

    PubMed  CAS  Google Scholar 

  • Matsuo K, Niwa M, Kurihara M, Shigematsu K, Yamashita S, Ozaki M, Nagataki S (1989) Receptor autoradiographic analysis of insulin-like growth factor-I (IGF-I) binding sites in rat forebrain and pituitary gland. Cell Mol Neurobiol 9:357–367

    Article  PubMed  CAS  Google Scholar 

  • Oomizu S, Takahashi S (1996) Insulin stimulates the proliferation of mouse anterior pituitary cells in vitro. Biomedical Res 17:365–371

    CAS  Google Scholar 

  • Oomizu S, Takeuchi S, Takahashi S (1998) Stimulatory effect of insulin-like growth factor I on proliferation of mouse pituitary cells in serum-free culture. J Endocrinol 157:53–62

    Article  PubMed  CAS  Google Scholar 

  • Oomizu S, Honda J, Takeuchi S, Kakeya T, Masui T, Takahashi S (2000) Transforming growth factor-alpha stimulates proliferation of mammotrophs and corticotrophs in the mouse pituitary. J Endocrinol 165:493–501

    Article  PubMed  CAS  Google Scholar 

  • Oomizu S, Chaturvedi K, Sarkar DK (2004) Folliculostellate cells determine the susceptibility of lactotropes to estradiol’s mitogenic action. Endocrinology 145:1473–1480

    Article  PubMed  CAS  Google Scholar 

  • Orgnero de Gaisán E, Maldonado C, Díaz Gavier MF, Aoki A (1997) Diversity of pituitary cells in primary culture. An immunocytochemical study. Annals Anat 179: 453–460

    Google Scholar 

  • Pazos F, Sanchez-Franco F, Balsa J, Escalada J, Cacicedo L (2004) Differential regulation of gonadotropins and glycoprotein hormone alpha-subunit by IGF-I in anterior pituitary cells from male rats. J Endocrinol Invest 27:670–675

    PubMed  CAS  Google Scholar 

  • Rosenfeld RG, Ceda G, Wilson DM, Dollar LA, Hoffman AR (1984) Characterization of high affinity receptors for insulin-like growth factors I and II on rat anterior pituitary cells. Endocrinology 114:1571–1575

    PubMed  CAS  Google Scholar 

  • Rosenfeld RG, Ceda G, Cutler CW, Dollar LA, Hoffman AR (1985) Insulin and insulin-like growth factor (somatomedin) receptors on cloned rat pituitary tumor cells. Endocrinology 117:2008–2016

    PubMed  CAS  Google Scholar 

  • Schechter J, Stauber C, Windle JJ, Mellon P (1995) Basic fibroblast growth factor: the neurotrophic factor influencing the ingrowth of neural tissue into the anterior pituitary of alpha-T7 transgenic mice? Neuroendocrinology 61:622–627

    PubMed  CAS  Google Scholar 

  • Sharma S, Oomizu S, Kakeya T, Masui T, Takeuchi S, Takahashi S (2003) Gene expression and the physiological role of transforming growth factor-alpha in the mouse pituitary. Zool Sci 20:83–89

    Article  PubMed  CAS  Google Scholar 

  • Soldani R, Cagnacci A, Yen SS (1994) Insulin, insulin-like growth factor I (IGF-I) and IGF-II enhance basal and gonadotrophin-releasing hormone-stimulated luteinizing hormone release from rat anterior pituitary cells in vitro. Eur J Endocrinol 131:641–645

    Article  PubMed  CAS  Google Scholar 

  • Steele-Perkins G, Turner J, Edman JC, Hari J, Pierce SB, Stover C, Rutter WJ, Roth RA (1988) Expression and characterization of a functional human insulin-like growth factor I receptor. J Biol Chem 263:11486–11492

    PubMed  CAS  Google Scholar 

  • Straus DS (1984) Growth-stimulatory actions of insulin in vitro and in vivo. Endocr Rev 5:356–369

    PubMed  CAS  Google Scholar 

  • Takahashi S, Oomizu S, Kobayashi Y (1994) Proliferation of pituitary cells in streptozotocin-induced diabetic mice: effect of insulin and estrogen. Zool Sci 11:445–449

    CAS  Google Scholar 

  • Takahashi S, Osawa T (1994) Decreased proliferation of pituitary cells of streptozotocin induced diabetic rats in response to estradiol-17-beta. Acta Anat 151:239–244

    Article  PubMed  CAS  Google Scholar 

  • Takahashi S, Oomizu S, Honda J, Takeuchi S (1997) Insulin-like growth factor I system in the mouse pituitary. In: Kawashima S, Kikuyama S (eds) Advances in comparative endocrinology. Proceedings of the XIII International Congress of Comparative Endocrinology. Monduzzi Ed, Bologna, pp 1123–1126

    Google Scholar 

  • Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, Henzel W, Le Bon T, Kathuria S, Chen E, Jacobs S, Francke U, Ramachandran J, Fujita-Yamaguchi Y (1986) Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 10:2503–2512

    Google Scholar 

  • Unger JW, Lange W (1997) Insulin receptors in the pituitary gland: morphological evidence for influence on opioid peptide-synthesizing cells. Cell Tissue Res 288:471–483

    Article  PubMed  CAS  Google Scholar 

  • Van Bael A, Denef C (1996) Evidence for a trophic action of the glycoprotein hormone alpha-subunit in rat pituitary. J Neuroendocrinol 8:99–102

    Article  PubMed  Google Scholar 

  • Wang YQ, Yuan R, Sun YP, Lee TJ, Shah GV (2003) Antiproliferative action of calcitonin on lactotrophs of the rat anterior pituitary gland: evidence for the involvement of transforming growth factor beta 1 in calcitonin action. Endocrinology 144:2164–2171

    Article  PubMed  CAS  Google Scholar 

  • Werther GA, Hogg A, Oldfield BJ, McKinley MJ, Figdor R, Allen AM, Mendelsohn FA (1987) Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology 121:1562–1570

    Article  PubMed  CAS  Google Scholar 

  • Wu X, Zhang R, Di A, Shan H, Xu R (1999) Effects of growth factors and estrogen on the proliferation and prolactin gene expression in anterior pituitary cells of rats. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 21:331–337

    PubMed  CAS  Google Scholar 

  • Yang D, Caraty A, Dupont J (2005) Molecular mechanisms involved in LH release by the ovine pituitary cells. Domest Anim Endocrinol 29:488–507

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Ms. Mercedes Guevara and Ms. Elena Pereyra for their excellent technical assistance and to Dr. Paul Hobson for revising the English of the manuscript.

Author information

Authors and Affiliations

  1. Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Haya de la Torre esq. E. Barros, X5000HRA, Córdoba, Argentina

    Silvina Gutiérrez, Jorge Humberto Mukdsi, Agustín Aoki, Alicia Inés Torres & Elsa Margarita Orgnero

  2. Department of Pathology, Duke University Medical Center, Durham, USA

    Alejandro Peralta Soler

Authors
  1. Silvina Gutiérrez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jorge Humberto Mukdsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Agustín Aoki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alicia Inés Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alejandro Peralta Soler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elsa Margarita Orgnero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elsa Margarita Orgnero.

Additional information

This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and the Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gutiérrez, S., Mukdsi, J.H., Aoki, A. et al. Ultrastructural immunolocalization of IGF-1 and insulin receptors in rat pituitary culture: evidence of a functional interaction between gonadotroph and lactotroph cells. Cell Tissue Res 327, 121–132 (2007). https://doi.org/10.1007/s00441-006-0283-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0283-4

Keywords

Search

Navigation