Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-11-9
pubmed:abstractText
Androgen and the androgen receptor (AR) have been shown to play critical roles in male fertility. Our previous data demonstrated that mice lacking AR (AR(-/y)) revealed incomplete germ cell development and lowered serum testosterone levels, which resulted in azoospermia and infertility. However, the consequences of AR loss in Leydig cells remain largely unknown. Using a Cre-LoxP conditional knockout strategy, we generated a tissue-specific knockout mouse (L-AR(-/y)) with the AR gene deleted by the anti-Müllerian hormone receptor-2 (Amhr2) promoter driven Cre expressed in Leydig cells. Phenotype analyses show that the outside appearance of L-AR(-/y) mice was indistinguishable from wild type mice (AR(+/y)), but with atrophied testes and epididymis. L-AR(-/y) mice were infertile, with spermatogenic arrest predominately at the round spermatid stage and no sperm could be detected in the epididymis. L-AR(-/y) mice also have lower serum testosterone concentrations and higher serum leuteinizing hormone and follicle-stimulating hormone concentrations than AR(+/y) mice. Further mechanistic studies demonstrated that hypotestosteronemia in L-AR(-/y) mice is not caused by reducing numbers of Leydig cells, but instead by the alterations of several key steroidogenic enzymes, including 17beta-HSD3, 3beta-HSD6, and P450c17. Together, L-AR(-/y) mice provide in vivo evidence that functional AR in Leydig cells is essential to maintain normal spermatogenesis, testosterone production, and required for normal male fertility.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1355-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
96-106
pubmed:dateRevised
2010-6-24
pubmed:meshHeading
pubmed-meshheading:17955388-17-Hydroxysteroid Dehydrogenases, pubmed-meshheading:17955388-3-Hydroxysteroid Dehydrogenases, pubmed-meshheading:17955388-Animals, pubmed-meshheading:17955388-Apoptosis, pubmed-meshheading:17955388-Azoospermia, pubmed-meshheading:17955388-Cell Proliferation, pubmed-meshheading:17955388-Epididymis, pubmed-meshheading:17955388-Female, pubmed-meshheading:17955388-Gene Expression, pubmed-meshheading:17955388-Leydig Cells, pubmed-meshheading:17955388-Male, pubmed-meshheading:17955388-Mice, pubmed-meshheading:17955388-Mice, Inbred C57BL, pubmed-meshheading:17955388-Mice, Knockout, pubmed-meshheading:17955388-Organ Size, pubmed-meshheading:17955388-Receptors, Androgen, pubmed-meshheading:17955388-Spermatids, pubmed-meshheading:17955388-Spermatogenesis, pubmed-meshheading:17955388-Steroid 17-alpha-Hydroxylase, pubmed-meshheading:17955388-Testis, pubmed-meshheading:17955388-Testosterone
pubmed:year
2007
pubmed:articleTitle
Infertility with defective spermatogenesis and steroidogenesis in male mice lacking androgen receptor in Leydig cells.
pubmed:affiliation
Department of Pathology, the Cancer Center, University of Rochester, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural