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

• Published in: Endocrinology (Philadelphia) Vol. 144; no. 1; pp. 138 - 145
• Main Authors: Baker, Paul J, Pakarinen, Pirjo, Huhtaniemi, Ilpo T, Abel, Margaret H, Charlton, Harry M, Kumar, T. Rajendra, O’Shaughnessy, Peter J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.01.2003; Oxford University Press
• Subjects: Animal models; Biological and medical sciences; Cell culture; Cell number; Cytochrome P450; Cytochromes P450; Follicle-stimulating hormone; Fundamental and applied biological sciences. Psychology; Hydroxysteroids; Luteinizing hormone; Mammalian male genital system; Morphology. Physiology; mRNA; Puberty; Receptors; Sertoli cells; Steroidogenic acute regulatory protein; Testosterone; Transfection; Vertebrates: reproduction; Cell function; Deficiency; Rodentia; Transgenic animal; Gonadotropin; Testicle; Male genital system; Leydig cell; Vertebrata; Mammalia; Adenohypophyseal hormone; Mouse; Differentiation; FSH receptor; Follicle stimulating hormone
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2002-220637

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 β-subunit (FSHβKO mice) or the FSH receptor (FSHRKO mice). Circulating LH levels were normal in adult FSHβKO mice, but were significantly increased in FSHRKO mice. Intratesticular testosterone levels increased normally in FSHβKO 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, 3β-hydroxysteroid dehydrogenase type VI, and steroidogenic acute regulatory protein in FSHRKO mice. Leydig cell number was normal in FSHβKO 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.