Endotoxin-induced changes in sex steroid hormone levels in male rats

Christeff, Névéna; Auclair, Marie-Claude; Benassayag, C.; Carli, A; Nunez, Emmanuel A.

doi:10.1016/0022-4731(87)90032-x

Cited by 46 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar decrease in testosterone was found in animals with endotoxemia and in septic patients treated in the ICU. 12,16 However, none of the patients in the present series suffered septic complications or organ dysfunction, and all recovered uneventfully and were discharged from hospital. Their uneventful clinical course was confirmed by the procalcitonin and SOFA-score values.…”

Section: Discussionmentioning

confidence: 95%

Gender-Specific Differences in Sex Hormones and Cytokines in Patients Undergoing Major Abdominal Surgery

et al. 2005

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 95%

Gender-Specific Differences in Sex Hormones and Cytokines in Patients Undergoing Major Abdominal Surgery

et al. 2005

View full text Add to dashboard Cite

show abstract

“…As already mentioned, estrogens are also known to modulate insulin resistance, an important contributor to outcomes during critical illness. Perhaps the best evidence of the pathophysiologic role of E2 in outcomes is that high doses of E2 pretreatment in mice increases mortality from subsequent lethal challenge with lipopolysaccharide (63) and that aromatase inhibitors decrease subsequent mortality from endotoxin in animals (6,64).…”

Section: Discussionmentioning

confidence: 99%

Estradiol is associated with mortality in critically ill trauma and surgical patients

May

Dossett

Norris

et al. 2008

Critical Care Medicine

View full text Add to dashboard Cite

Objective: Sexual dimorphism (variation in outcome related to sex) after trauma-hemorrhage and sepsis is well documented in animals, with the pro-estrus state being proinflammatory and associated with a survival advantage. Although some observational studies confirm this pattern in humans, others demonstrate no difference in mortality. Estrogens are important modulators of the inflammatory response and insulin resistance in humans and have been linked to increased mortality during sepsis. Our objective was to determine whether sex hormone levels were associated with outcomes in critically ill surgical patients. Design: Prospective cohort.Patients: A total of 301 adult critically ill or injured surgical patients remaining in the intensive care unit for ≥48 hrs at two academic medical centers. Interventions: None.Measurements: Blood was collected 48 hrs after intensive care unit admission and assayed for sex hormones (estradiol, testosterone, prolactin, and progesterone) and cytokines (tumor necrosis factor-α and interleukin-1, -2, -4, -6, -8, and -10). Demographic and outcome data were also collected.Main Results: Estradiol was significantly higher in nonsurvivors (p < .001). Analysis by quartiles of estradiol demonstrated greater than a three-fold increase in the mortality rate for the highest vs. the lowest estradiol quartiles (29% vs. 8%, p < .001). Estradiol was also higher in nonsurvivors. An estradiol level of 100 pg/mL was associated with an odds ratio for death of 4.60 (95% confidence interval, 1.56-13.0) compared with a reference estradiol level of 45 pg/mL. Conclusions:We conclude that serum estradiol correlates with mortality in critically ill and injured surgical patients and discuss potential mechanisms for this observation. Keywordsestradiol; mortality; trauma; critical care; sexual dimorphism; aromatase For information regarding this article, E-mail: addison.may@vanderbilt.eduThe authors have not disclosed any potential conflicts of interest.This work was performed at Vanderbilt University Medical Center, Nashville, TN, and the Hospitals of the University of Virginia Health System, Charlottesville, VA. All authors took part in the interpretation of the findings and contributed to the preparation of the manuscript. In-hospital death after a severe traumatic, surgical, or septic insult often results from the sequential development of organ dysfunction (multiple organ dysfunction syndrome, or MODS). Although progression to MODS largely depends on the magnitude of tissue injury, considerable variation exists in an individual's susceptibility to this syndrome (1-3). Sex has been suggested as one determinant of this variability. NIH Public AccessIn animal models, the pro-estrous state is proinflammatory, with improved survival after untreated trauma-hemorrhage and sepsis, whereas the proandrogenic state leads to immune depression and decreased survival (4-10). Observational studies in humans have been less conclusive (9,. Although a number of human observational studies confirm this pattern, othe...

show abstract

“…(Tulassay et al 1970) or i.v. (Christeff et al 1987) with endotoxin, a substance known to stimulate TNF production and (ii) recombinant human TNF administration by continuous infusion to male rats induced severe seminiferous epithelium damage (Mealy et al 1990). Although it has been shown that the disruption of the spermatogenetic processs in testes exposed to increased levels of TNF could be related to a decrease in testosterone levels (Li et al 1995, Mauduit et al 1991, 1998, our present findings support the possibility that this spermatogenic arrest could also result from defects in detoxification processes in the gonad.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-alpha inhibits glutathione S-transferase-alpha expression in cultured porcine Sertoli cells

Benbrahim‐Tallaa

Boussouar²,

Rey³

et al. 2002

Journal of Endocrinology

View full text Add to dashboard Cite

Glutathione S-transferases (GSTs) are a family of soluble enzymes of detoxification that use reduced glutathione in conjugation and reduction reactions. Toxic electrophiles are substrates for the GSTs. GST is expressed at high levels in different tissues such as the testis. Among the different GSTs present in the testis, GST is specifically expressed in Leydig and Sertoli cells known to be under the control of hormonal and local regulatory factors. The present study investigated the regulatory action of tumor necrosis factor-(TNF ) on basal and hormone (FSH and testosterone)-stimulated GST expression in cultured Sertoli cells. Treatment with TNF (0-20 ng/ml, 48 h) induced a decrease in basal GST mRNA levels in a dose-dependent manner (fivefold decrease; P<0·001). The maximal and half maximal effects were observed at 20 ng/ml and 7 ng/ml respectively. The inhibitory effect of TNF was also time-dependent with a maximal inhibitory effect (threefold decrease; P<0·001) observed at 48 h. The inhibitory effect of the cytokine was also observed on basal GST protein (28 kDa) levels. TNF also inhibited the hormone-stimulated GST expression in Sertoli cells. The treatment of cultured Sertoli cells with both FSH and TNF (100 ng/ml and 10 ng/ml respectively, 48 h) resulted in a complete suppression of the stimulatory action of FSH on GST mRNA levels. Similarly, in Sertoli cells treated with testosterone or its non-aromatizable metabolite dihydrotestosterone (100 ng/ml, 24 h), TNF reduced the hormone-stimulated GST mRNA and protein levels. TNF inhibited basal GST expression without affecting mRNA stability. Indeed, the decay curves (mRNA half-life time=18 h) for the GST basal mRNA levels in Sertoli cells was similar in the absence or presence of TNF (10 ng/ml, 48 h). Testosterone increased GST mRNA without affecting the enzyme mRNA stability. TNF antagonized the androgen-stimulated GST mRNA levels without affecting the enzyme mRNA stability, suggesting that the interaction between the androgen and the cytokine is mostly exerted at a transcriptional level. FSH increased GST mRNA levels through an increase in mRNA stability (increased mRNA half-life times to 119 h). TNF antagonized the stimulatory effect of FSH on GST mRNA levels by antagonizing the stabilizing effect exerted by the hormone on GST mRNA. Together, these results suggest that the increase in the cytokine levels within the testis would alter the detoxification processes against genotoxic products during spermatogenesis.

show abstract

Endotoxin-induced changes in sex steroid hormone levels in male rats

Cited by 46 publications

References 18 publications

Gender-Specific Differences in Sex Hormones and Cytokines in Patients Undergoing Major Abdominal Surgery

Gender-Specific Differences in Sex Hormones and Cytokines in Patients Undergoing Major Abdominal Surgery

Estradiol is associated with mortality in critically ill trauma and surgical patients

Tumor necrosis factor-alpha inhibits glutathione S-transferase-alpha expression in cultured porcine Sertoli cells

Contact Info

Product

Resources

About