This paper provides a systematic, multidimensional demographic analysis of the degree to which negative economic consequences of population aging can be mitigated by changes in migration and ...labor-force participation. Using a microsimulation population projection model accounting for 13 individual characteristics including education and immigration-related variables, we built scenarios of future changes in labor-force participation, migration volumes, and their educational composition and speed of integration for the 28 European Union (EU) member states. We study the consequences in terms of the conventional age-dependency ratio, the labor-force dependency ratio, and the productivity-weighted labor-force dependency ratio using education as a proxy of productivity, which accounts for the fact that not all individuals are equality productive in society. The results show that in terms of the more sophisticated ratios, population aging looks less daunting than when only considering age structure. In terms of policy options, lifting laborforce participation among the general population as in Sweden, and education-selective migration if accompanied by high integration, could even improve economic dependency. On the other hand, high immigration volumes combined with both low education and integration leads to increasing economic dependency. This shows the high stakes involved with integration outcomes under high migration volumes.
There is an increasing trend to apply gas chromatography combined with mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS/MS) assay methods to large-scale ...epidemiologic studies for the measurement of serum sex steroids. These methods are generally considered the gold standard for sex steroid measurements because of their accuracy, sensitivity, turnaround time, and ability to assess a more complete panel of steroid metabolites in the same run. In this report, we evaluated the precision, including within-batch (intra) and between-batch (inter) reproducibility, of steroid hormone measurements determined by GC-MS and LC-MS/MS assays and RIA and compared measurements among these methods. Specifically, 282 overnight fasting serum samples from 20 male volunteers were analyzed for 12 steroid metabolites by GC-MS or LC-MS/MS in one lab over a 4-month period. Six of the analytes were also measured by RIA in another lab. Unconjugated hormones, including testosterone, dihydrotestosterone, dehydroepiandrosterone, androstenedione, androst-5-ene-3beta,17beta-diol, estrone, and estradiol, were measured by GC-MS, whereas conjugated hormones, including DHEA sulfate, androsterone glucuronide, 5alpha-androstane-3alpha,17beta-diol 3-glucuronide, 5alpha-androstane-3alpha,17beta-diol 17-glucuronide, and estrone sulfate, were measured by LC-MS/MS. A subset of these hormones, including testosterone, dihydrotestosterone, androstenedione, 5alpha-androstane-3alpha,17beta-diol 17-glucuronide, estrone, and estradiol, were also measured by RIA following extraction and chromatography. We used the coefficient of variation (CV) and the intraclass correlation coefficient (ICC) to assess within- and between-batch assay variations. For the 12 analytes measured by GC-MS or LC-MS/MS, CVs and ICCs for within- and between-batch measurements were similar, with CVs ranging from 6.1% to 21.4% and ICCs ranging from 87.6% to 99.2%. The six analytes measured by RIA had good CVs and ICCs, with CVs <10% and ICCs >70% (range, 71.7-99.7%). For the six metabolites that were measured by both methods, the CVs were similar, whereas the ICCs were generally higher with the GC-MS method. The absolute values for each analyte measured by RIA and GC-MS differed, with RIAs usually yielding markedly higher levels than GC-MS, although the Pearson and Spearman correlation coefficients for these six analytes were near one and all were significant (P < 0.001). Our results show that RIA, GC-MS, and LC-MS/MS assays for androgens and estrogens in the two labs included in the study have good reproducibility, as measured by small CVs (<15%) and high ICCs (>80%), with the exception of estradiol (71.7%) when measured by RIA. Despite substantial differences in absolute measurements of sex steroid hormones by RIA and MS methods, correlations between the two assays for the six sex steroids measured in the two labs were high (>0.9). However, it is important for future large epidemiologic studies to incorporate MS with high reproducibility and specificity to measure a more complete profile of androgen and estrogen metabolites to clarify the role of sex steroids in prostate cancer.
•All active androgens in women are made from DHEA in each peripheral tissue independently from the rest of the body.•Each peripheral tissue has about 30 steroidogenic and steroid-inactivating enzymes ...to control the tissue-specific transformation of DHEA.•The androgens made intracellularly in peripheral tissues are inactivated locally with no significant release of active androgens in the circulation.•Women synthesize about 50% as much androgens as made in men of the same age.•Serum testosterone remains at biologically inactive concentrations below 260pg/ml, thus avoiding systemic exposure.
The objective is to review how the cell-specific amounts of intracellular androgens are all made in women from circulating dehydroepiandrosterone (DHEA) in each peripheral tissue, independently from the rest of the body. Following 500 million years of evolution, approximately three dozen cell-specific intracrine enzymes have been engineered in human peripheral tissues whereby the inactive sex steroid precursor DHEA mainly of adrenal origin is transformed into the appropriate minute intracellular amounts of androgens. These intracellular androgens are inactivated in the same cells, with no biologically significant release of active androgens in the circulation. The best estimate is that approximately 50% as much androgens are synthesized in women, compared to men of the same age. The problem with DHEA, however, the exclusive source of androgens in women of all ages, is that DHEA secretion has already decreased by an average of 60% at time of menopause and continues to decrease thereafter. The human-specific and highly sophisticated mechanisms of intracrinology permit each cell to control androgen availability according to its own needs independently from the remaining of the body. Such a mechanism is completely different from classical endocrinology well understood in men where testosterone of testicular origin is transported through the blood and has indiscriminate access to the androgen receptor (AR) in all AR-containing cells of the body. In men, both the endocrine and intracrine mechanisms are in operation while, in women, only the intracrine mechanisms responsible for intracellular formation from DHEA provide androgens.
•Glucuronidation is the major androgen metabolic pathway in the human prostate.•UGT2B15 and UGT2B17 enzymes control androgen inactivation in prostate cells.•UGT2B15 and/or UGT2B17 polymorphisms have ...deep impact on androgen elimination.•UGT2B15 and/or UGT2B17 activities influence prostate cancer evolution.
In the prostate, approximately 50% of androgens are from adrenal steroids, mainly dehydroepiandrosterone (DHEA), its sulfate and androstenedione. These compounds are converted first into testosterone, and then into the active hormone dihydrotestosterone (DHT). After having activated the androgen receptor (AR), DHT is reduced into androstane-3α-DIOL (3α-DIOL) and androsterone (ADT), which are subsequently converted into 2 inactive and easily excretable metabolites: 3α-DIOL-17glucuronide (3α-DIOL-17G) and ADT-3glucuronide (ADT-3G). The formation of these last derivatives through the glucuronidation reaction involves 2 UDP-glucuronosyltransferase (UGT) enzymes, namely UGT2B15 and UGT2B17. The present review article aims at providing a comprehensive view of the physiological and pharmacological importance of these 2 enzymes for the control of androgen homeostasis. We will resume: (i) how UGT2B15 and UGT2B17 contribute to androgen elimination; (ii) how their glucuronidation capacity influences the androgen signaling pathway in prostate cells; (iii) how they contribute to the anti-proliferative properties of AR antagonists in prostate cancer cells; and (iv) how AR and its spliced variants regulate the UGT2B15 and/or UGT2B17 genes expression. Finally, whether the unexploited AR-UGT axis could serve as a prognostic maker or a pharmacological target for novel therapeutics in the treatment of prostate cancer is also discussed.
This article is part of a special issue entitled ‘Essential role of DHEA’.
BACKGROUND Population ageing is unavoidable in Europe, but perhaps its impact on labor force is not. In the context of a new demographic regime of high immigration and low fertility, differentials in ...labor force participation and educational attainment can be more consequential for the labor force than either the number of immigrants or structure of the overall population. OBJECTIVE The objective of this paper is to investigate how improvements in both educational attainment (especially among children with a low educated mother or an immigration background) and labor force participation (especially of women and immigrants) could impact the future labor force in the European Union. METHODS We used a microsimulation model called CEPAM-Mic to project the labor force of EU28 countries. CEPAM-Mic incorporates heterogeneity among different groups and allows the development of alternative scenarios concerning educational attainment and labor force participation of disadvantaged groups. RESULTS Removing inequalities between subgroups in educational attainment and labor force participation drastically changes the prospective labor force size and labor force dependency ratio (LFDR) in the EU. Assuming perfect equality, the anticipated decline in the labor force size reduces by 54%, while the expected increase in the LFDR narrows by 70%. CONCLUSION Population aging is a destiny in large part driven by past demographic behaviors, but its anticipated consequences in terms of labor force size and labor force dependency ratio may be avoidable. CONTRIBUTION This paper features a policy-oriented use of microsimulation population projections. The alternative scenarios developed go beyond traditional demographic scenarios that can only set assumptions on fertility, mortality and migration.
In the human prostate, dihydrotestosterone (DHT) – the natural androgen having the highest affinity for the androgen receptor – is not released directly into the systemic circulation from peripheral ...target tissues but it is rather converted in situ into two metabolites which have a low affinity for the androgen receptor: androsterone (ADT) and androstane-3α,17β-diol (3α-DIOL). Several clinical observations indicate that these two androgen metabolites are further inactivated in the prostate by glucuronidation. In the human, the family of UDP-glucuronosyltransferase (UGT) enzymes comprises 18 members in three subfamilies: UGT1A, UGT2A and UGT2B. Identification of the substrates for each member has revealed that three UGT2B enzymes are mainly responsible for DHT, ADT and 3α-DIOL glucuronidation: UGT2B7, UGT2B15 and UGT2B17. Tissue distribution and cellular localization of UGT2B transcripts and proteins clearly indicate that only UGT2B15 and UGT2B17 are expressed in the prostate. Using the human prostate carcinoma LNCaP cell line, it was shown that UGT2B expression and activity are negatively regulated by several factors, including androgens. On the other hand, inhibition of UGT2B115/17 expression by small interfering RNA (siRNA) resulted in an induced response to DHT of androgen-receptor target genes such as PSA, KLK4, NKX3.1, TMPRSS2, SLC16A6 and VEGF. It is suggested that the conjugating activity of UGT enzymes in androgen target tissues is a mechanism for modulating the action of steroids and/or protecting the tissues from deleterious high concentrations of androgens.
BACKGROUND In most developed countries the demographic regime is characterised by low fertility, high immigration, and population ageing. This regime impacts on the size of the labour force ...population, the ethno-cultural composition, and potential productivity. OBJECTIVE We examine the prospective impacts of two sociodemographic changes, namely increasing education and increasing immigration levels, on the size and skills of the workforce aged 25 to 64 years old for the time period 2011-2061. METHODS We use microsimulation models to project the population of Austria and Canada by age, sex, and several other socioeconomic and ethno-cultural dimensions. Using 'what-if scenarios, we measure the impact of different immigration rates and immigrant selection patterns on the size and average literacy skills of the projected workforce. We also examine the potential effects of different assumptions about future educational attainment on the projection outcomes. RESULTS The results show that the volume of immigration heavily influences the expansion of the workforce .In terms of education among the general population, the rise in educational attainment is positively correlated with higher skill levels. However, increased immigration can override the effect that increasing education levels have on advancing workforce skills. CONTRIBUTION This paper shows the extent to which Austria and Canada have adopted diametrically opposed strategies regarding the future development of their workforces. Assuming that current policy goals hold true in the coming decades, Austria is likely to rely on a higher-skilled but declining (in size) workforce, whereas Canada will rely on a fast-growing but less-skilled and more culturally diversified workforce.
Uridine diphosphate-glucuronosyltransferase 2 (UGT2)B15 and B17 enzymes conjugate dihydrotestosterone (DHT) and its metabolites androstane-3α, 17β-diol (3α-DIOL) and androsterone (ADT). The presence ...of UGT2B15/B17 in the epithelial cells of the human prostate has been clearly demonstrated, and significant 3α-DIOL glucuronide and ADT-glucuronide concentrations have been detected in this tissue. The human androgen-dependent cancer cell line, LNCaP, expresses UGT2B15 and -B17 and is also capable of conjugating androgens. To assess the impact of these two genes in the inactivation of androgens in LNCaP cells, their expression was inhibited using RNA interference. The efficient inhibitory effects of a UGT2B15/B17 small interfering RNA (siRNA) probe was established by the 70% reduction of these UGT mRNA levels, which was further confirmed at the protein levels. The glucuronidation of dihydrotestosterone (DHT), 3α-DIOL, and ADT by LNCaP cell homogenates was reduced by more than 75% in UGT2B15/B17 siRNA-transfected LNCaP cells when compared with cells transfected with a non-target probe. In UGT2B15/B17-deficient LNCaP cells, we observe a stronger response to DHT than in control cells, as determined by cell proliferation and expression of eight known androgen-sensitive genes. As expected, the amounts of DHT in cell culture media from control cells were significantly lower than that from UGT2B15/B17 siRNA-treated cells, which was caused by a higher conversion to its corresponding glucuronide derivative. Taken together these data support the idea that UGT2B15 and -B17 are critical enzymes for the local inactivation of androgens and that glucuronidation is a major determinant of androgen action in prostate cells.
Many developed countries have turned to immigration in order to mitigate the consequences of population aging, particularly the expected decline in the labor force population. Yet, few projection ...models take in consideration explicitly the differentials in labor force participation of population sub-groups. This paper describes the labor force participation module of CEPAM-Mic, which is a microsimulation model that projects several demographic, ethnocultural, and socioeconomic dimensions of the EU28 member countries population. Then, the microsimulation model is used to project EU labor force population for the period 2015–2060 under different scenarios illustrating how implementing sex- and country-specific dynamics of immigrants’ integration may affect the future labor force in terms of size, rates, and gender composition. We estimated the parameters of the labor force module using logistic regressions based on the EU-Labour Force Survey (EU-LFS). In addition to age, sex, and education, immigrant-related variables are also included, such as immigrant status, place of birth, age at immigration, and duration of residence in the estimation of the probability of being active. Our results demonstrate the importance of taking into account differentials in labor force participation of population sub-groups when asserting the potential of immigration as a tool for managing population aging. In the European context, adding immigration differentials in labor force participation affects mainly downward the number of female immigrants in the labor force, while smaller differences are observed for male immigrants. An increase in immigration levels leads obviously to an increase in the total labor force size, but may also widen gender inequalities in labor force participation and has limited impact on the total labor force participation rate. Our findings suggest that relying on immigration as a tool to alleviate economic issues arising from population aging must imperatively be accompanied by strong and efficient measures to promote a full economic integration of immigrants.
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