Interleukin-1 Inhibits Leydig Cell Steroidogenesis in Primary Culture*

Calkins, Jo H.; Sigel, M. Michael; Nankin, Howard R.; Lin, T.

doi:10.1210/endo-123-3-1605

Cited by 198 publications

(82 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Insulinlike growth factor-I (IGF-I) enhances LH/hCGstimulated testosterone formation (Lin 1996), and high levels of IGF-I are expressed in Leydig cells (Lin et al 1986). In primary cultures of Leydig cells, interleukin-1 (IL-1) is a potent inhibitor of testosterone formation (Calkins et al 1988(Calkins et al , 1990a. IL-1 blocks hCG-stimulated cAMP formation and cytochrome P450 side-chain cleavage (P450 scc) mRNA expression (Lin et al 1991a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression and regulation of glucose transporter 8 in rat Leydig cells

Chen

Nagpal²,

Lin

2003

Journal of Endocrinology

View full text Add to dashboard Cite

Basal and LH/human chorionic gonadotropin (hCG)-stimulated testosterone formation by Leydig cells is dependent on ambient glucose levels. Inhibition of glucose uptake is associated with decreased testosterone formation. Recently, glucose transporter 8 (GLUT8) has been shown to be highly expressed in the testis. In the present study, we have investigated the expression and regulation of the GLUT8 gene in rat Leydig cells. Primers were designed by using sequences that are not conserved in GLUT1 to GLUT5 and that contain the glycosylation region of GLUT8. This yielded an amplicon of 186 bp. The tissue-specific expression experiments in adult rat (55-to 65-day-old) tissues revealed that GLUT8 is expressed predominantly in the testis, in smaller amounts in heart and kidney, and in negligible amounts in liver and spleen. Furthermore, GLUT8 mRNA was found to be highly expressed in crude interstitial cells, Leydig cells and testicular and epididymal germ cells. In prepubertal rat (20-day-old) tissues, GLUT8 expression was comparatively much lower than in the adult rat tissues. By comparative RT-PCR, hCG caused dose-and timedependent increases of GLUT8 mRNA levels. hCG and IGF-I had synergistic effects on GLUT8 mRNA and protein expression. GLUT1 and GLUT3 were also found to be expressed in Leydig cells. However, neither GLUT1 nor GLUT3 were affected by treatments with hCG, IGF-I or hCG and IGF-I combined. The addition of murine interleukin-1 (mIL-1 ; 10 ng/ml), murine tumor necrosis factor-(mTNF-; 10 ng/ml), murine interferon-(mIFN-; 500 U/ml) separately or in combination decreased hCG-induced GLUT8 mRNA levels significantly. In conclusion, GLUT8 mRNA in Leydig cells was positively regulated by hCG and IGF-I and downregulated by cytokines, mIL-1 , mTNF-and mIFN-. These results indicate that hCG, growth factors and cytokines affect Leydig cell steroidogenesis by modulating GLUT8 expression.

show abstract

Section: Introductionmentioning

confidence: 99%

“…IL-1 blocks hCG-induced cAMP formation and P450 scc expression and acts as a potent inhibitor of testosterone formation (Calkins et al 1988, 1990b, Lin et al 1991b. In insulin-sensitive tissues, cytokines downregulate GLUT4 expression (Long & Pekala 1996) and up-regulate GLUT1 expression (Stephens et al 1992).…”

mentioning

confidence: 99%

Expression and regulation of glucose transporter 8 in rat Leydig cells

Chen

Nagpal²,

Lin

2003

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Plusieurs facteurs inhibent la s~cr6tion de testost6rone induite par la LH dans les cellules de Leydig : le TGF~ [34,46], l'activine A [25,39], l'ILla [7,41] et le TNFa [8,40,44,84]. Cependant, ces facteurs n'agissent pas sur les m~mes 6tapes biochimiques de la st6ro~dogen~se.…”

Section: A) Facteurs Inhibiteursunclassified

Rôle des facteurs de croissance et cytokines dans le testicule normal et pathologique

Mauduit

Hamamah

Loras

et al. 1997

Androl.

View full text Add to dashboard Cite

RESUME L'6tude de la st6rilit6 masculine a trouv6 depuis 4 ans un regain d'int6r6t avec l'av~nement d'une nouvelle technique pour le traitement de rinfertilit6 masculine, l'injection intracytoplasmique d'un spermatozoide dans l'ovocyte (ICSI). N6anmoins, l'6tude des caract6ristiques du sperme demeure le maitre examen dans r6valuation de la fertilit6 masculine. II constitue le reflet de l'activit6 testiculaire et des 6v6nements post-gonadiques, en particulier, la maturation 6pididymaire. Ces processus sont pour la plupart, non seulement sous le contr61e du syst~me neuroendocrinien, mais aussi, sous le contr61e de facteurs locaux tels que les facteurs de croissance et les cytokines. Dans cette revue, nous pr6-sentons, dans une premiere partie, les donn6es montrant le r61e crucial que jouent les facteurs locaux sur la formation du testicule fatal mais aussi sur les fonctions diff6renci6es de la gonade comme la st6roidogen~se et la spermatogen~se. Dans une seconde partie, nous pr6sentons les donn6es obtenues dans le cadre de l'exploration de l'homme infertile, ainsi que les effets in vitro des facteurs locaux sur le pouvoir f6condant des spermatozoides. Ces derni~res donn6es sont encore fragmentaires et l'utilisation des facteurs de croissance et des cytokines dans le domaine des st6rilit6s dites idiopathiques n'en est qu'~ ses d6buts. Enfin, dans le cadre d'une d6marche prospective, nous indiquons quelques voies de recherche qui nous semblent int6res-santes concernant l'6tude des facteurs de croissance et des cytokines dans les st6rilit6 masculines.

show abstract

“…We and others have reported previously that IL-1 is a potent inhibitor of luteinizing hormone/human choriogonadotropin (hCG)-induced androgen formation by Leydig cells (Calkins et al 1988, Verhoeven et al 1988, Hales 1992, Mauduit et al 1992. IL-1 decreases hCG-stimulated cAMP and testosterone formation (Calkins et al 1988). IL-1 also reduces 8-bromo-cAMP-induced testosterone formation and hCG-induced cytochrome P450 side-chain cleavage (P450 scc) mRNA expression in rat Leydig cells (Calkins et al 1988, Lin et al 1991.…”

Section: Introductionmentioning

confidence: 97%

“…Increased plasma IL-1 concentration and reduced serum testosterone levels are frequently found in patients with critical illness and septicemia (Vogel et al 1985, Woolf et al, 1985, Cannon et al 1990). We and others have reported previously that IL-1 is a potent inhibitor of luteinizing hormone/human choriogonadotropin (hCG)-induced androgen formation by Leydig cells (Calkins et al 1988, Verhoeven et al 1988, Hales 1992, Mauduit et al 1992. IL-1 decreases hCG-stimulated cAMP and testosterone formation (Calkins et al 1988).…”

Section: Introductionmentioning

confidence: 98%

Interleukin-1 inhibits Leydig cell steroidogenesis without affecting steroidogenic acute regulatory protein messenger ribonucleic acid or protein levels

Lin

Wang²,

Stocco³

1998

Journal of Endocrinology

View full text Add to dashboard Cite

The rate-limiting step of steroidogenesis is the transport of the substrate cholesterol from the outer to the inner mitochondrial membrane which involves a cycloheximide-sensitive newly synthesized protein. A protein believed to carry out this function was recently cloned from MA-10 mouse Leydig tumor cells and named the steroidogenic acute regulatory protein (StAR). In the present study, we evaluated the expression and regulation of StAR in primary cultures of rat Leydig cells. StAR mRNA was expressed in Leydig cells as two major transcripts of 3·8 and 1·7 kb and one minor transcript of 1·2 kb. Induction of StAR mRNA transcripts could be detected as early as 30 min after the addition of human choriogonadotropin (hCG) with peak levels attained between 2 and 4 h. hCG in concentrations of 0·1-10 ng/ml caused a dose-dependent increase in StAR mRNA expression. hCG administered at a dose of 10 ng/ml increased the 3·8 kb StAR mRNA level about 14-fold and the 1·7 kb StAR mRNA level about 13·6-fold. hCG-stimulated StAR mRNA was associated with increased StAR protein levels as determined by immunoblot analysis (a 4·5-fold increase). Murine interleukin-1 (mIL-1 ) at a concentration of 100 ng/ml inhibited hCGinduced cytochrome P450 side-chain cleavage (P450 scc) mRNA expression and testosterone formation almost completely. Interestingly, mIL-1 had no effect on hCGinduced StAR mRNA or protein levels. Furthermore, mIL-1 (10 ng/ml) decreased conversion of (22R)-hydroxycholesterol to testosterone while the conversion of pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and androstenedione to testosterone were not affected. These results indicate that the major inhibitory effect of IL-1 on Leydig cell function occurs at the level of P450 scc.

show abstract

Interleukin-1 Inhibits Leydig Cell Steroidogenesis in Primary Culture*

Cited by 198 publications

References 32 publications

Expression and regulation of glucose transporter 8 in rat Leydig cells

Expression and regulation of glucose transporter 8 in rat Leydig cells

Rôle des facteurs de croissance et cytokines dans le testicule normal et pathologique

Interleukin-1 inhibits Leydig cell steroidogenesis without affecting steroidogenic acute regulatory protein messenger ribonucleic acid or protein levels

Contact Info

Product

Resources

About