Failure of normal Leydig cell development in follicle-stimulating hormone (FSH) receptor-deficient mice, but not FSHbeta-deficient mice: role for constitutive FSH receptor activity
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 beta-subunit (FSHbetaKO mice) or the FSH receptor (FSHRKO mice). Circulating LH levels were normal in adult FSHb...
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Published in | Endocrinology (Philadelphia) Vol. 144; no. 1; pp. 138 - 145 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.01.2003
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Abstract | 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 beta-subunit (FSHbetaKO mice) or the FSH receptor (FSHRKO mice). Circulating LH levels were normal in adult FSHbetaKO mice, but were significantly increased in FSHRKO mice. Intratesticular testosterone levels increased normally in FSHbetaKO 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, 3beta-hydroxysteroid dehydrogenase type VI, and steroidogenic acute regulatory protein in FSHRKO mice. Leydig cell number was normal in FSHbetaKO 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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AbstractList | 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 beta-subunit (FSHbetaKO mice) or the FSH receptor (FSHRKO mice). Circulating LH levels were normal in adult FSHbetaKO mice, but were significantly increased in FSHRKO mice. Intratesticular testosterone levels increased normally in FSHbetaKO 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, 3beta-hydroxysteroid dehydrogenase type VI, and steroidogenic acute regulatory protein in FSHRKO mice. Leydig cell number was normal in FSHbetaKO 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. |
Author | Pakarinen, Pirjo O'Shaughnessy, Peter J Baker, Paul J Huhtaniemi, Ilpo T Kumar, T Rajendra Abel, Margaret H Charlton, Harry M |
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Snippet | 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... |
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SubjectTerms | Animals Cyclic AMP - metabolism Follicle Stimulating Hormone, beta Subunit - deficiency Follicle Stimulating Hormone, beta Subunit - genetics Follicle Stimulating Hormone, beta Subunit - physiology Gene Expression Leydig Cells - chemistry Leydig Cells - physiology Male Mice Mice, Inbred C57BL Mice, Knockout Point Mutation Progesterone - biosynthesis Receptors, FSH - deficiency Receptors, FSH - genetics Receptors, FSH - physiology RNA, Messenger - analysis Sertoli Cells - physiology Testis - chemistry Testis - growth & development Testosterone - analysis Transfection |
Title | Failure of normal Leydig cell development in follicle-stimulating hormone (FSH) receptor-deficient mice, but not FSHbeta-deficient mice: role for constitutive FSH receptor activity |
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