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

被引:66
作者
Baker, PJ
Pakarinen, P
Huhtaniemi, IT
Abel, MH
Charlton, HM
Kumar, TR
O'Shaughnessy, PJ
机构
[1] Univ Glasgow, Sch Vet, Dept Vet Preclin Studies, Inst Comparat Med, Glasgow G61 1QH, Lanark, Scotland
[2] Univ Turku, Dept Physiol, FIN-20520 Turku, Finland
[3] Univ Oxford, Dept Human Anat & Genet, Oxford OX1 3QX, England
[4] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA
[5] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
D O I
10.1210/en.2002-220637
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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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页码:138 / 145
页数:8
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