Article

Upregulation of Human Chorionic Gonadotrophin-Induced Steroidogenic Acute Regulatory Protein by Insulin-Like Growth Factor-I in Rat Leydig Cells

University of South Carolina, Columbia, South Carolina, United States
Endocrine (Impact Factor: 3.88). 03/1998; 8(1):73-8. DOI: 10.1385/ENDO:8:1:73
Source: PubMed

ABSTRACT

Insulin-like growth factor-I (IGF-I) plays an essential role in reproductive function. Leydig cells express specific IGF-I receptors, and IGF-I enhances human chorionic gonadorphin (hCG)-induced testosterone formation. In the present study, we evaluate the effect of IGF-I on the gene expression and protein levels of steroidogenic acute regulatory protein (StAR), the rate-limiting step in steroidogenesis. StAR mRNA is expressed in rat Leydig cells as two major transcripts of 3.8 and 1.7 kb. StAR mRNA levels (both 3.8 and 1.7 kb) were markedly induced about 20-fold by hCG (10 ng/mL). Concomitant addition of IGF-I (50 or 100 ng/mL) and hCG (10 ng/mL) resulted in significant increases in StAR and cytochrome P450 side-chain cleavage (P450scc) mRNA levels, whereas lower doses of IGF-I (1 or 10 ng/ mL) had small effects. Synergistic effects of IGF-I and hCG on StAR mRNA levels were confirmed by ribonuclease protection assay (RPA). IGF-I (100 ng/mL) enhanced hCG- and 20 OH-cholesterol + hCG-induced testosterone formation, whereas the conversions of pregnenolone, 17-OH pregnenolone, dehydroepiandrosterone, and androstenedione to testosterone were not affected. This suggests that the major effect of IGF-I is at the steps of StAR and P450scc, whereas other steroidogenic enzymes are not affected. To evaluate whether increased StAR mRNA levels induced by IGF-I and hCG are associated with increased StAR protein levels, we carried out Western blot analyses. Basal StAR protein levels were low after 24 h in culture. hCG (10 ng/mL) increased StAR protein by 4.5-fold. In the presence of IGF-I (100 ng/mL), hCG-induced StAR protein levels were further increased. In conclusion, our present study demonstrated that IGF-I enhances Leydig cell steroidogenesis by upregulating hCG-induced StAR gene expression and protein production.

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    • "Another interesting feature of the increased testosterone levels in the present study is that the induction of P450scc in low and medium NR-DE exposed groups was also very similar to that of StAR or plasma testosterone except for the 3-month exposure. The induction of P450scc has also been considered to be up-regulated by IGF-I in Leydig cells (Lin et al., 1998). In addition, the expression of P450scc was significantly lower in IGF-null mice than wild-type mice (Wang et al., 2003). "
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    ABSTRACT: Diesel exhaust emission contains a high amount of nano-sized particles and is considered to be systemically distributed in the body. However, few studies about the effects of nanoparticle rich-diesel exhaust (NR-DE) on liver have been reported. The present investigation focuses on the effects of NR-DE on livers in rats, especially concerning inflammation and lipid metabolism. Male F344 rats were exposed to fresh air or low (24 ± 7 µg/m(3) ), medium (39 ± 4 µg/m(3) ) and high (138 ± 20 µg/m(3) ) concentrations of NR-DE for 1, 2, or 3 months (5 hours/day, 5 days/week). Exposure to both medium and high concentrations of NR-DE for one month increased plasma asparate aminotransferase and alanine aminotransferase activities, while only high concentrations increased plasma interleukin-6 and hepatic nuclear factor kappa B (NFκB), suggesting that activation of hepatic inflammatory signaling took place. Although these exposures elevated peroxisome proliferator-activated receptor (PPAR) α levels or its binding activity to the response element, neither activated PPARα-target genes such as β-oxidative enzymes nor inhibited NFκB elevation. Thus, NR-DE may contain some materials that inhibit PPARα activation in relation to lipid metabolism and inflammation. Taken together, NR-DE exposure at one month may cause inflammation; however, this finding may not be observed after a longer exposure period. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.
    No preview · Article · Sep 2015 · Environmental Toxicology
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    • "Another interesting feature of the increased testosterone levels in the present study is that the induction of P450scc in low and medium NR-DE exposed groups was also very similar to that of StAR or plasma testosterone except for the 3-month exposure. The induction of P450scc has also been considered to be up-regulated by IGF-I in Leydig cells (Lin et al., 1998). In addition, the expression of P450scc was significantly lower in IGF-null mice than wild-type mice (Wang et al., 2003). "
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    ABSTRACT: Nanoparticle-rich diesel exhaust (NR-DE) has potentially adverse effects on testicular steroidogenesis. However, it is unclear whether NR-DE influences steroidogenic systems in the brain. To investigate the effect of NR-DE on hippocampal steroidogenesis of adult male rats in comparison with its effect on the testis. F344 male rats (8-week-old) were randomly divided into four groups (n = 8 or 9 per group) and exposed to clean air with 4.6 ± 3.2 μg/m(3) in mass concentration, NR-DE with 38 ± 3 μg/m(3) (a level nearly equivalent to the environmental standard in Japan (low NR-DE)), NR-DE with 149 ± 8 μg/m(3) (high NR-DE), or filtered diesel exhaust with 3.1 ± 1.9 μg/m(3) (F-DE), for 5 hours/day, 5 days/week, for 1, 2 or 3 months. F-DE was prepared by removing only particulate matters from high NR-DE with an HEPA filter. Exposures to the high NR-DE for 1 month, and low NR-DE for 2 months, significantly increased or tended to increase plasma and testicular testosterone levels compared to clean air exposure, which might have resulted from the increased expression of mRNA of steroidogenic acute regulatory protein and its protein in the testes of rats. In the hippocampus, high NR-DE exposure for 1 month significantly increased the androstendione level compared to the clean air exposure, while no significant difference was observed in the steroidogenesis between fresh air exposure and any exposure to NR-DE or F-DE. NR-DE may influence steroidogenic enzymes in the testis, but not those in the hippocampus.
    Full-text · Article · Jun 2012 · Inhalation Toxicology
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    • "Another interesting feature of the increased testosterone levels in the present study is that the induction of P450scc in low and medium NR-DE exposed groups was also very similar to that of StAR or plasma testosterone except for the 3-month exposure. The induction of P450scc has also been considered to be up-regulated by IGF-I in Leydig cells (Lin et al., 1998). In addition, the expression of P450scc was significantly lower in IGF-null mice than wild-type mice (Wang et al., 2003). "
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    ABSTRACT: We previously reported that exposure to low (22.5+/-0.2 nm in diameter, 15.4+/-1.0 microg/m(3) in mass weight, 2.27x10(5)/cm(3) in mean number concentration), and medium (26.1+/-0.5 nm, 36.4+/-1.2 microg/m(3), 5.11x10(5)/cm(3)) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for 1 and 2 months (5 h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1+/-0.5 nm, 168.8+/-2.7 microg/m(3), 1.36x10(6)/cm(3)) did not. The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for 1 and 2 months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats, in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for 1 month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats. These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity, which may, in part, be regulated by increasing StAR and P450scc expressions via GH signalling.
    Full-text · Article · Sep 2009 · Toxicology Letters
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