PMID- 8319591
OWN - NLM
STAT- MEDLINE
DCOM- 19930803
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 133
IP  - 1
DP  - 1993 Jul
TI  - Tumor necrosis factor-alpha antagonizes follicle-stimulating hormone action in 
      cultured Sertoli cells.
PG  - 69-76
AB  - In the present study, we have tested the effect of tumor necrosis factor-alpha 
      (TNF alpha) on FSH action in cultured purified Sertoli cells isolated from 
      immature porcine testes. FSH action was evaluated through three different 
      parameters (aromatase activity, lactate production, and alpha-inhibin 
      production). TNF alpha was shown to reduce (about 40-60% decrease) FSH-stimulated 
      but not basal aromatase activity (evaluated through the conversion of 
      testosterone into estradiol) in a dose- and time-dependent manner. The maximal 
      and half-maximal (IC50) effects were observed with 6 ng/ml (3.5 x 10(-10) M) and 
      0.6 ng/ml (3.5 x 10(-11) M), respectively, after a long-term (72 h) treatment. 
      TNF alpha (20 ng/ml) also inhibited Sertoli cell aromatase activity when 
      stimulated with 8-bromo-cAMP (0.01-3 mM, 72 h) instead of FSH, suggesting that 
      the antigonadotropin action of the cytokine is probably exerted at a step located 
      beyond cAMP formation. The inhibitory effect of TNF alpha was not limited to the 
      action of FSH on aromatase activity but also extended to the gonadotropin action 
      on lactate and inhibin-alpha chain production in Sertoli cells. As for 
      FSH-induced aromatase activity, TNF alpha reduced FSH-stimulated lactate 
      accumulation with an IC50 of 0.6 ng/ml, after a long-term (72 h) treatment. 
      Again, the cytokine reduced lactate production stimulated by 8-bromo-cAMP, 
      suggesting that TNF alpha antagonistic action against FSH is exerted at post-cAMP 
      levels. Finally, TNF alpha exerted a more pronounced inhibitory effect (> 90% 
      inhibition) on alpha-inhibin than on inhibin heterodimer production. These 
      inhibitory effects of TNF alpha on the gonadotropin action are probably exerted 
      directly on Sertoli cells, since TNF alpha high affinity binding sites 
      (dissociation constant approximately 5.3 x 10(-10) M) are present in primary 
      cultures of purified porcine Sertoli cells. Altogether, the present findings show 
      that TNF alpha antagonizes FSH action on Sertoli cell functions such as aromatase 
      activity and lactate and alpha-inhibin production. Such an inhibitory effect is 
      probably exerted at a biochemical step(s) located beyond cAMP generation.
FAU - Mauduit, C
AU  - Mauduit C
AD  - INSERM CJF 90-08, Groupe de Recherches sur les Communications Cellulaires, 
      Hopital Sainte Eugenie, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
FAU - Jaspar, J M
AU  - Jaspar JM
FAU - Poncelet, E
AU  - Poncelet E
FAU - Charlet, C
AU  - Charlet C
FAU - Revol, A
AU  - Revol A
FAU - Franchimont, P
AU  - Franchimont P
FAU - Benahmed, M
AU  - Benahmed M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Lactates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 57285-09-3 (Inhibins)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 1.14.14.1 (Aromatase)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
MH  - Animals
MH  - Aromatase/metabolism
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Follicle Stimulating Hormone/*antagonists & inhibitors/pharmacology
MH  - Inhibins/biosynthesis
MH  - Kinetics
MH  - Lactates/biosynthesis
MH  - Lactic Acid
MH  - Male
MH  - Sertoli Cells/drug effects/enzymology/*metabolism
MH  - Swine
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
EDAT- 1993/07/01 00:00
MHDA- 1993/07/01 00:01
CRDT- 1993/07/01 00:00
PHST- 1993/07/01 00:00 [pubmed]
PHST- 1993/07/01 00:01 [medline]
PHST- 1993/07/01 00:00 [entrez]
AID - 10.1210/endo.133.1.8319591 [doi]
PST - ppublish
SO  - Endocrinology. 1993 Jul;133(1):69-76. doi: 10.1210/endo.133.1.8319591.