Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice
UMass Chan Affiliations
Department of PediatricsDepartment of Cell Biology
Information Services, Academic Computing Services
Document Type
Journal ArticlePublication Date
2005-02-12Keywords
Age FactorsAnimals
Anti-Mullerian Hormone
Body Weight
Cells, Cultured
Glycoproteins
Leydig Cells
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Organ Size
Phosphoproteins
RNA, Messenger
Sexual Maturation
Testicular Hormones
Testis
Testosterone
Biostatistics
Cell Biology
Life Sciences
Medicine and Health Sciences
Statistics and Probability
Metadata
Show full item recordAbstract
Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both basal and human chorionic gonadotropin (hCG)-stimulated testosterone concentrations were similar. Purified Leydig cells from pubertal MIS-KO mice had lower testosterone but higher androstanediol and androstenedione production rates. In contrast, testosterone, androstanediol, and androstenedione production rates were all lower in adult MIS-KO Leydig cells. Steroidogenic acute regulatory protein expression was lower in pubertal MIS-KO mice compared with WT, whereas 17beta-hydroxy-steroid dehydrogenase and 5alpha-reductase were greater, and P450c17 and P450scc were similar. The expression of steroidogenic acute regulatory protein and 17beta-hydroxysteroid dehydrogenase was lower in adult MIS-KO mice, whereas that of 5alpha-reductase, P450c17, and P450scc was similar. Collectively, these results suggest that in the absence of MIS, Leydig cells remain less differentiated, causing an altered intratesticular androgen milieu that may contribute to the infertility of MIS-KO mice. In immature mice, this deficit in steroidogenic capacity appears to be mediated by a direct loss of MIS action in Leydig cells as well as by indirect effects via the hypothalamic-pituitary-gonadal axis.Source
Endocrinology. 2005 Feb;146(2):589-95. Epub 2004 Oct 28. Link to article on publisher's siteDOI
10.1210/en.2004-0646Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35324PubMed ID
15514087Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1210/en.2004-0646