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Failure of Normal Leydig Cell Development in Follicle-Stimulating Hormone (FSH) Receptor-Deficient Mice, But Not FSHß-Deficient Mice: Role for Constitutive FSH Receptor Activity

Institute of Comparative Medicine, University of Glasgow Veterinary School (P.J.B., P.J.O.), Glasgow, Scotland G61 1QH, United Kingdom; Department of Physiology, University of Turku (P.P., I.T.H.), 20520, Turku, Finland; Department of Human Anatomy and Genetics, University of Oxford (M.H.A., H.M.C.), Oxford OX1 3QX, United Kingdom; and Departments of Pathology and Molecular and Cellular Biology, Baylor College of Medicine (T.R.K.), Houston, Texas 77030

Address all correspondence and requests for reprints to: Prof. P. J. O’Shaughnessy, Institute of Comparative Medicine, Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, United Kingdom. E-mail: p.j.o'shaughnessy{at}vet.gla.ac.uk.

Previous studies have suggested that FSH may be involved in regulation of Leydig cell function. We have examined this directly using two mouse models with null mutations in either the FSH ß-subunit (FSHßKO mice) or the FSH receptor (FSHRKO mice). Circulating LH levels were normal in adult FSHßKO mice, but were significantly increased in FSHRKO mice. Intratesticular testosterone levels increased normally in FSHßKO mice from birth to adulthood, whereas testosterone levels in FSHRKO mice failed to increase normally after puberty and were significantly reduced in adult animals. This was associated with reduced levels of mRNA encoding cytochrome P450 side-chain cleavage, 3ß-hydroxysteroid dehydrogenase type VI, and steroidogenic acute regulatory protein in FSHRKO mice. Leydig cell number was normal in FSHßKO mice during development, but in FSHRKO mice Leydig cell number increased slowly after puberty and was significantly reduced in the adult animal. Transfection studies showed that the FSHR exhibits constitutive activity in the absence of agonist stimulation. The results indicate, therefore, that Sertoli cells regulate the development of Leydig cell number and that constitutive activity within the FSHR is sufficient to stimulate this process. The presence of the hormone itself is not required when circulating LH levels are adequate.

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