PMID- 8726216
OWN - NLM
STAT- MEDLINE
DCOM- 19961009
LR  - 20131121
IS  - 0091-7370 (Print)
IS  - 0091-7370 (Linking)
VI  - 26
IP  - 3
DP  - 1996 May-Jun
TI  - Sphingomyelinase inhibits in vitro Leydig cell function.
PG  - 234-42
AB  - Activation of the immune system has profound effects on endocrine function which 
      are mediated by cytokines including tumor necrosis factor-alpha (TNF alpha). In 
      vitro, TNF alpha has been shown to directly inhibit Leydig cell testosterone (T) 
      production, but the mechanism of this effect is still unclear. Recent studies 
      using cultured human fibroblasts have shown that TNF alpha stimulates the 
      activity of neutral sphingomyelinase (SMase) which hydrolyses sphingomyelin (SM) 
      generating ceramide and changing membrane components including cholesterol. The 
      cellular affects of increased SMase activity have been reproduced in vitro by the 
      addition of exogenous SMase. In cultured fibroblasts, exogenous SMase decreases 
      cholesterol synthesis. These findings led us to hypothesize that SMase might be 
      important in the regulation of steroid hormone synthesis. To our knowledge, no 
      previous studies have investigated this possibility. To test this hypothesis, rat 
      Leydig cell enriched cultures were incubated in media containing SMase (0.1 to 
      100 mU/ml) or in control media. SMase significantly decreased basal and human 
      chorionic gonadotropin (hCG) stimulated T production. SMase also decreased hCG 
      binding and hCG stimulated adenosine 3':5'-cyclic monophosphate (cAMP). 
      N-acetyl-sphingosine (0.1 to 10 microM), a water soluble ceramide, was used to 
      determine whether or not the effects of SMase could be reproduced by ceramide 
      addition. N-acetyl-sphingosine had only slight effects on basal T and cAMP, and 
      no effect on hCG binding or hCG stimulated T or cAMP. These data suggest the 
      metabolism of membrane sphingomyelin may be an important regulatory pathway in 
      the control of Leydig cell function.
FAU - Degnan, B M
AU  - Degnan BM
AD  - Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC 20307, 
      USA.
FAU - Bourdelat-Parks, B
AU  - Bourdelat-Parks B
FAU - Daniel, A
AU  - Daniel A
FAU - Salata, K
AU  - Salata K
FAU - Francis, G L
AU  - Francis GL
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Ann Clin Lab Sci
JT  - Annals of clinical and laboratory science
JID - 0410247
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (N-acetylsphingosine)
RN  - 0 (Receptors, LH)
RN  - 3XMK78S47O (Testosterone)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Bucladesine/pharmacology
MH  - Cell Survival/drug effects
MH  - Chorionic Gonadotropin/metabolism/pharmacology
MH  - Cyclic AMP/metabolism
MH  - Leydig Cells/drug effects/*metabolism
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, LH/metabolism
MH  - Sphingomyelin Phosphodiesterase/metabolism/*pharmacology
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - Testosterone/biosynthesis
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
PST - ppublish
SO  - Ann Clin Lab Sci. 1996 May-Jun;26(3):234-42.