The murine Niemann-Pick type C lesion affects testosterone production

Calvin F. Roff, Jerome F. Strauss, Ehud Goldin, Howard Jaffe, Marc C. Patterson, George C. Agritellis, Anna Maria Hibbs, Mark Garfield, Roscoe O. Brady, Peter G. Pentchev

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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, 20α-hydroxycholesterol, and pregnenolone compared to testosterone release by normal mouse testes under identical conditions. Ultrastuctural 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 β-glucuronidase activity was also underexpressed. Seminal vesicle mass and β-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 α2-μ-globulin, glutathione S-transferase-π, 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.

Original languageEnglish (US)
Pages (from-to)2913-2923
Number of pages11
JournalEndocrinology
Volume133
Issue number6
StatePublished - Dec 1993
Externally publishedYes

Fingerprint

Testosterone
Testis
Seminal Vesicles
Glucuronidase
Puberty
Proteins
Androgens
Selenium-Binding Proteins
Carbonic Anhydrase III
8-Bromo Cyclic Adenosine Monophosphate
Pregnenolone
Leydig Cells
Inclusion Bodies
Globulins
Lysosomes
Glutathione Transferase
Endoplasmic Reticulum
Cholesterol
Kidney

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Roff, C. F., Strauss, J. F., Goldin, E., Jaffe, H., Patterson, M. C., Agritellis, G. C., ... Pentchev, P. G. (1993). The murine Niemann-Pick type C lesion affects testosterone production. Endocrinology, 133(6), 2913-2923.

The murine Niemann-Pick type C lesion affects testosterone production. / Roff, Calvin F.; Strauss, Jerome F.; Goldin, Ehud; Jaffe, Howard; Patterson, Marc C.; Agritellis, George C.; Hibbs, Anna Maria; Garfield, Mark; Brady, Roscoe O.; Pentchev, Peter G.

In: Endocrinology, Vol. 133, No. 6, 12.1993, p. 2913-2923.

Research output: Contribution to journalArticle

Roff, CF, Strauss, JF, Goldin, E, Jaffe, H, Patterson, MC, Agritellis, GC, Hibbs, AM, Garfield, M, Brady, RO & Pentchev, PG 1993, 'The murine Niemann-Pick type C lesion affects testosterone production', Endocrinology, vol. 133, no. 6, pp. 2913-2923.
Roff CF, Strauss JF, Goldin E, Jaffe H, Patterson MC, Agritellis GC et al. The murine Niemann-Pick type C lesion affects testosterone production. Endocrinology. 1993 Dec;133(6):2913-2923.
Roff, Calvin F. ; Strauss, Jerome F. ; Goldin, Ehud ; Jaffe, Howard ; Patterson, Marc C. ; Agritellis, George C. ; Hibbs, Anna Maria ; Garfield, Mark ; Brady, Roscoe O. ; Pentchev, Peter G. / The murine Niemann-Pick type C lesion affects testosterone production. In: Endocrinology. 1993 ; Vol. 133, No. 6. pp. 2913-2923.
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