The murine Niemann-Pick type C lesion affects testosterone production
| Autor: | Jerome F. Strauss, Roscoe O. Brady, Mark Garfield, Anna Maria Hibbs, Calvin F. Roff, Ehud Goldin, Peter G. Pentchev, George C. Agritellis, M. C. Patterson, Howard Jaffe |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Aging medicine.medical_specialty medicine.drug_class Molecular Sequence Data Genitalia Male In Vitro Techniques Testicle Biology Kidney Lesion Mice Endocrinology Seminal vesicle Reference Values Internal medicine Lipid droplet Testis otorhinolaryngologic diseases medicine Animals Testosterone Amino Acid Sequence Glucuronidase Niemann-Pick Diseases Mice Inbred BALB C Androgen medicine.disease Mice Mutant Strains stomatognathic diseases medicine.anatomical_structure Liver Pregnenolone medicine.symptom Peptides Niemann–Pick disease medicine.drug |
| Zdroj: | Endocrinology. 133:2913-2923 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.133.6.8243319 |
| Popis: | We have determined the effects of the Niemann-Pick type C (NPC) lesion, which impairs transport of cholesterol from lysosomes, on the androgenic status of male NPC mice. The mice have low serum testosterone levels resulting from decreased testosterone secretion. Testosterone secretion is reduced in NPC mouse testes incubated with 8-bromo-cAMP, 20 alpha-hydroxycholesterol, and pregnenolone compared to testosterone release by normal mouse testes under identical conditions. Ultrastructural examination of testes revealed a paucity of lipid droplets, extensive accumulation of inclusion bodies, and distorted endoplasmic reticulum in Leydig cells of adult NPC mice. The hypoandrogenemia caused systemic deficiencies in NPC mice. Seminal vesicles, a testosterone-responsive tissue, were underdeveloped in NPC male mice. The testosterone-responsive kidney beta-glucuronidase activity was also underexpressed. Seminal vesicle mass and beta-glucuronidase activity were increased by testosterone treatment of NPC mice. Many hepatic proteins, identified by microsequencing, were also deficient in NPC male mice. Levels of alpha 2-mu-globulin, glutathione S-transferase-pi, carbonic anhydrase-III, and selenium-binding protein increased in normal male mice during puberty, but did not increase in the NPC male mice. Based on the increases in protein expression during puberty, differential expression in males and females, and the reported involvement of androgens in regulating expression of some of these proteins, deficient expression of most of these proteins in male NPC mice appears to result from low testosterone levels. We conclude that a defect in testicular testosterone production in NPC male mice causes a pleiotropic deficiency in androgen-sensitive expression of proteins in various organs. |
| Databáze: | OpenAIRE |
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