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Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: a study on hCG overexpressing transgenic mice

Oncogene volume 24, pages 7301–7309 (2005)Cite this article

Abstract

We have previously demonstrated that male transgenic (TG) mice overexpressing human chorionic gonadotropin (hCG+) develop reproductive organ defects, but no tumors, in adult age. In this study, the effects of persistently elevated hCG were followed in TG males between day 5 postpartum and adulthood. Leydig cell (LC) adenomas were found in prepubertal mice, most prominently at the age of 10 days, but not in adult age. Serum testosterone concentrations were significantly increased in TG males at all ages studied. The phenotype of the prepubertal hCG+ males resembled that found in boys upon expression of constitutively activating luteinizing hormone (LH) receptor mutations. The temporal expression patterns of the fetal LC marker gene, thrombospondin 2, and those of adult LCs, hydroxysteroid dehydrogenase-6, delta5-3-beta and prostaglandin D synthase, were similar in wild-type and hCG+ males. Hence, the postnatal adenomas resemble functionally fetal LCs, and only these cells are susceptible to hCG-induced tumorigenesis. Our findings demonstrate a novel intriguing difference between the fetal and adult LC populations and provide further insight into the potential tumorigenic effects of gonadotropins.

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Acknowledgements

We thank Ms J Lahtinen and Ms T Laiho for their skilful technical assistance. This work was supported by grants from the Academy of Finland, The Finnish Cancer Society, the Sigrid Jusélius Foundation, the Turku Graduate School for Biomedical Sciences and the Wellcome Trust.

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Authors and Affiliations

  1. Department of Physiology, University of Turku, Turku, FIN-20520, Finland

    Petteri Ahtiainen, Susana B Rulli, Ramin Shariatmadari, Jorma Toppari, Matti Poutanen & Ilpo T Huhtaniemi

  2. Turku Graduate School of Biomedical Science, University of Turku, Turku, FIN-20520, Finland

    Petteri Ahtiainen

  3. Institute of Biology and Experimental Medicine-CONICET, Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina

    Susana B Rulli

  4. Laboratory of Electron Microscopy, University of Turku, Turku, FIN-20520, Finland

    Lauri J Pelliniemi

  5. Department of Pediatrics, University of Turku, Turku, FIN-20520, Finland

    Jorma Toppari

  6. Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

    Ilpo T Huhtaniemi

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  1. Petteri Ahtiainen
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Correspondence to Ilpo T Huhtaniemi.

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Ahtiainen, P., Rulli, S., Shariatmadari, R. et al. Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level: a study on hCG overexpressing transgenic mice. Oncogene 24, 7301–7309 (2005). https://doi.org/10.1038/sj.onc.1208893

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