1. ¹Department of Physiology, University of Turku, FIN-20520 Turku, Finland
2. ²Turku Graduate School of Biomedical Science, University of Turku, FIN-20520 Turku, Finland
3. ³Institute of Biology and Experimental Medicine-CONICET, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
4. ⁴Laboratory of Electron Microscopy, University of Turku, FIN-20520 Turku, Finland
5. ⁵Department of Pediatrics, University of Turku, FIN-20520 Turku, Finland
6. ⁶Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK

Correspondence: IT Huhtaniemi, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. E-mail: ilpo.huhtaniemi@imperial.ac.uk

Received 26 January 2005; Revised 24 May 2005; Accepted 31 May 2005; Published online 11 July 2005.

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.