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

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 mic...

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Published inEndocrinology (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
LanguageEnglish
Published Bethesda, MD Endocrine Society 01.01.2003
Oxford University Press
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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 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.
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 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.
Author Pakarinen, Pirjo
Baker, Paul J
O’Shaughnessy, Peter J
Kumar, T. Rajendra
Huhtaniemi, Ilpo T
Abel, Margaret H
Charlton, Harry M
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Issue 1
Keywords Cell function
Deficiency
Rodentia
Transgenic animal
Gonadotropin
Testicle
Male genital system
Leydig cell
Vertebrata
Mammalia
Adenohypophyseal hormone
Mouse
Differentiation
FSH receptor
Follicle stimulating hormone
Language English
License CC BY 4.0
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PublicationTitle Endocrinology (Philadelphia)
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Oxford University Press
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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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StartPage 138
SubjectTerms 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
Title 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
URI http://dx.doi.org/10.1210/en.2002-220637
https://www.proquest.com/docview/3130532349
Volume 144
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