Context
Earlier studies have investigated the role of obesity‐related inflammation and endogenous sex hormones in men. The role of interleukin‐6 (IL‐6) and C‐reactive protein (CRP) with testosterone ...and sex hormone binding globulin (SHBG) levels in men is still debated.
Objective
To investigate the independent association between levels of high sensitivity CRP (hsCRP) and IL‐6 with endogenous sex hormones in men.
Design
Cross‐sectional observational study using data from the Multi‐Ethnic Study of Atherosclerosis.
Patients or Other Participants
A community‐based sample of 3212 men aged 45–84 years was included. After exclusions, 3041 men remained for the analyses.
Main Outcome Measure(s)
Serum concentrations of testosterone, SHBG, hsCRP, IL‐6, and sTNFR were measured from the baseline exam. Multivariable linear regressions were used to examine the association of inflammatory markers with sex hormones.
Results
An inverse association was found between levels of hsCRP and levels of testosterone and SHBG, even after adjustment for confounders and IL‐6 (Total Testosterone; B = −0.14, Bioavailable Testosterone; B = −0.06, and SHBG; B = −0.66). Similar results were found for IL‐6, although a positive association was found for SHBG (B = 0.95). Notably, an inverse association was found for IL‐6 with bioavailable testosterone in African Americans and Hispanic Americans aged 45–54 years. No associations were found for sTNFR and endogenous sex hormones.
Conclusion
Our results indicate that inflammatory markers have independent associations with levels of testosterone (total and bioavailable) and furthermore, appear to associate differently with SHBG levels.
Atrazine is currently one of the most commonly used agrochemicals in the United States and elsewhere. Here, we studied the immunoexpression of molecular markers of mammalian testicular functions: ...androgen receptor (AR), promyelocytic leukemia zinc finger (PLZF), GDNF family receptor alpha-1 (GFRA1), VASA/DDX4 (DEAD-Box Helicase 4) as well as the levels of intratesticular and intra-epididymal estradiol (E2) and dihydrotestosterone (DHT), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL-1β and IL-6, IL-10) and testicular chemokines (CXCL-1, CCL-2 and CCL3) in BalB/c mice after a sub-acute gavage treatment with a gonado-toxin, atrazine (50 mg/kg body wt.) for three days. We found high numbers of AR immunopositive Sertoli cells and low numbers of GFRA1, PLZF and VASA/DDX4-positive germ cells in the seminiferous tubule regions of the testes. While TNF-α level in the testes fell and remained unchanged in the epididymides, IFN-γ levels in the testes remained constant but increased in the epididymides. E2 and DHT concentrations remained unaltered in the testes but were changed in the epididymides. There were no significant changes in the levels of interleukins in the testis and epididymis. Intratesticular chemokines were also not significantly altered, except for CCL-4, which was increased in the testis. Light microscopy of the epididymis showed detached epithelium and some detached cells in the lumen. It is concluded that atrazine changed the inflammatory status of the gonads and highlighted Sertoli and undifferentiated spermatogonia as important targets for atrazine's toxic effects in the testis of mice. Concerning the epididymis, atrazine altered the epididymal hormonal concentrations and promoted histopathological modifications in its parenchyma.
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•Acute exposure to atrazine has detrimental effects on the testis and epididymis.•Atrazine decreased VASA/DDX4, GFRA1 and PLZF expression in germ cells.•Atrazine increased AR expression in Sertoli cells.•Atrazine increased aromatase immunofluorescence in epididymides.•Epididymides are highly affected by atrazine's inflammatory and hormonal effects.
Sex hormone binding globulin (SHBG) is a hormone binding protein which plays an important role in regulating the transport and availability of biologically active androgens and estradiol to target ...cells and used to calculate free testosterone concentrations.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed, featuring an albumin removal step followed by a tryptic digestion. After a reduction step with dithiothreitol and alkylation with iodoacetamide three signature peptides were used for the quantification of SHBG.
The method enables the quantification of serum and plasma SHBG over the clinically relevant range of 200-20,000 ng/mL and was validated according to the most recent guidelines. The LC-MS/MS method correlates well with the Abbott Alinity immunoassay (R
>0.95), but the LC-MS/MS results are on average 16-17% lower than the immunoassay results, which is consistent for all three signature peptides.
The LC-MS/MS method which includes an albumin depletion step allows quantification of SHBG in serum and plasma without an immunocapture step at clinically relevant SHBG levels, thus contributing to better lab-to-lab consistency of results.
Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, ...termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER â» breast cancer, AR â» prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5â²- and 3â²-SHOT-RNAs, corresponding to 5â²- and 3â²-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3â²-end, respectively. By devising a âcP-RNA-seqâ method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5â²-SHOT-RNAs. Furthermore, 5â²-SHOT-RNA, but not 3â²-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets.
Although transfer RNAs (tRNAs) are best known as adapter molecules essential for translation, recent biochemical and computational evidence has led to a previously unexpected conceptual consensus that tRNAs are not always end products but can further serve as a source of small functional RNAs. Here we report that a novel type of tRNA-derived small RNA, termed SHOT-RNAs, are specifically and abundantly expressed in sex hormone-dependent breast and prostate cancers. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated cleavage of the anticodon loop, which is promoted by sex hormones and their receptors. We identified the complete repertoire of SHOT-RNAs, and also found their functional significance in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis.
New Findings
What is the topic of this review?
We review sex differences within physiological systems implicated in exercise performance; specifically, how they integrate to determine metabolic ...thresholds and fatigability. Thereafter, we discuss the implications that these sex differences might have for long‐term adaptation to exercise.
What advances does it highlight?
The review collates evidence from recent physiological studies that have investigated sex as a biological variable, demonstrating that the physiological response to equivalent ‘dosages’ of exercise is not the same in males and females; thus, highlighting the need to research diversity in physiological responses to interventions.
The anatomical and physiological differences between males and females are thought to determine differences in the limits of human performance. The notion of studying sex as a biological variable has recently been emphasized in the biosciences as a vital step in enhancing human health. In this review, we contend that the effects of biological sex on acute and chronic responses must be studied and accounted for when prescribing aerobic exercise, much like any intervention targeting the optimization of physiological function. Emerging evidence suggests that the response of physiological systems to exercise differs between males and females, potentially mediating the beneficial effects in healthy and clinical populations. We highlight evidence that integrative metabolic thresholds during exercise are influenced by phenotypical sex differences throughout many physiological systems. Furthermore, we discuss evidence that female skeletal muscle is more resistant to fatigue elicited by equivalent dosages of high‐intensity exercise. How the different acute responses affect the long‐term trainability of males and females is considered, with discussion about tailoring exercise to the characteristics of the individual presented within the context of biological sex. Finally, we highlight the influence of endogenous and exogenous sex hormones on physiological responses to exercise in females. Sex is one of many mediating influences on the outcomes of exercise, and with careful experimental designs, physiologists can advance the collective understanding of diversity in physiology and optimize outcomes for both sexes.
Outcomes and susceptibility to out-of-hospital cardiac arrest (OHCA) are known to differ by sex, yet little is known about changes in sex hormones after OHCA. We sought to determine the trajectory of ...sex hormones after OHCA and their association to survival and neurological outcome.
Plasma samples were collected from those that survived to hospital admission at four time points (1, 6, 24, and 48 hours) and estrone, estradiol, progesterone, and testosterone concentrations were quantified via liquid chromatography-mass spectrometry. Trends in hormones were plotted over time by sex and outcomes. The association between sex, hormone levels with survival and neurological outcome (cerebral performance category 1-2 indicating good outcome and 3-5 for poor outcome) were determined using generalized estimating equation models.
Of the 94 OHCA patients, 50 were males and 44 females, with a mean age of 61.3 (+15.7) years. Despite older age and lower BCPR in females compared to males, females had higher proportion of good neurological outcome compared to males. Over the 48 hours, estrone increased, testosterone decreased, and estradiol and progesterone remained flat. Survivors had lower levels of estrone at all time points but only at early time points for estradiol, progesterone and testosterone. Lower estrone level predicted survival at discharge, even after adjusting for time, sex, age, and hormones independently (β=-3.38, 95% CI= -5.71, -0.85). Females had better neurological scores compared to males after adjusting for estrone (β=1.27, 95% CI= 0.01, 2.53) and estradiol (β=2.92, 95% CI= 1.13, 4.70).
Survivors and those with favorable neurological outcome had lower trend in estrone. The sex hormone estrone, present in both males and females, may be a predictor of survival. When adjusted for estrogens, female sex had better neurological recovery compared to males. The difference in neurological outcome by sex is not explained by estrogens. However, these finding open the door for exploration of other sex-specific pathways in resuscitation after OHCA.
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