HIV infection and STI in the trans population: a critical review.

BACKGROUND: Based on the scarcity of existing data in France, the objective of this critical review of the literature is to assess the available data on HIV infection and STIs and their major risk factors among the transgender population around the world. METHODS: Papers published from 1986 to 2008 were selected in PubMed and Ovid using the following keywords in the title: "female-to-male", "male-to-female", "transsexualism", "Gender Identity Disorder", and the keywords "transsexualism", and "transgender". A second manual selection was carried out with the keywords "HIV", "AIDS", and "STI". A few non-indexed references were also included. Overall, 124 references were selected, most of them reporting studies in the United States. RESULTS: This review provides evidence of the difficulties related to establishing a consistent and consensual definition of the transgender population and its different subgroups and also to identifying its sociodemographic characteristics. It shows the diversity of risk factors and the risk for HIV infection and STIs, which endanger the different subgroups of this population to different degrees. Belonging to an ethnic minority, international migration, social instability, and participation in sex work are the major risk factors for this population. Taking into account that all transgender individuals are not exposed in the same proportions to HIV and STI risks, it is recommended that more social and epidemiological work be developed, which would more accurately consider all the characteristics of this population and the high-risk situations to which it is exposed.

Metabolomic, proteomic and biophysical analyses of Arabidopsis thaliana cells exposed to a caesium stress. Influence of potassium supply.

The incorporation and localisation of 133Cs in a plant cellular model and the metabolic response induced were analysed as a function of external K concentration using a multidisciplinary approach. Sucrose-fed photosynthetic Arabidopsis thaliana suspension cells, grown in a K-containing or K-depleted medium, were submitted to a 1 mM Cs stress. Cell growth, strongly diminished in absence of K, was not influenced by Cs. In contrast, the chlorophyll content, affected by a Cs stress superposed to K depletion, did not vary under the sole K depletion. The uptake of Cs was monitored in vivo using 133Cs NMR spectroscopy while the final K and Cs concentrations were determined using atomic absorption spectrometry. Cs absorption rate and final concentration increased in a K-depleted external medium; in vivo NMR revealed that intracellular Cs was distributed in two kinds of compartment. Synchrotron X-ray fluorescence microscopy indicated that one could be the chloroplasts. In parallel, the cellular response to the Cs stress was analysed using proteomic and metabolic profiling. Proteins up- and down-regulated in response to Cs, in presence of K+ or not, were analysed by 2D gel electrophoresis and identified by mass spectrometry. No salient feature was detected excepting the overexpression of antioxidant enzymes, a common response of Arabidopsis cells stressed whether by Cs or by K-depletion. 13C and 31P NMR analysis of acid extracts showed that the metabolome impact of the Cs stress was also a function of the K nutrition. These analyses suggested that sugar metabolism and glycolytic fluxes were affected in a way depending upon the medium content in K+. Metabolic flux measurements using 13C labelling would be an elegant way to pursue on this line. Using our experimental system, a progressively stronger Cs stress might point out other specific responses elicited by Cs.

Conversion of dehydroepiandrosterone sulfate at physiological plasma concentration into estrogens in MCF-7 cells.

Metabolism of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and androstene-3,17-dione (delta(4)) was performed at their physiological plasma concentrations in MCF-7 cell cultures (1 microM, 10 and 2 nM, respectively). Final metabolic products of these steroids were separated by HPLC-radioactive flow detection and identified by LC/MS or MS/MS. Typical and specific mass fragmentation spectra identified the presence of estrone (E(1)), 17beta-estradiol (E(2)), delta(4), DHEA, 5-androstene-3beta,17beta-diol (delta(5)), and testosterone as principal DHEAS metabolites. Other steroids, such as androstenedione, androsterone, and DHEA fatty acid esters at very low concentrations (from pM to nM), were also obtained after steroid incubation. This highly specific method allowed us to conclude whether a metabolite and enzymatic activity of interest were present in MCF-7 cells or not. We also showed that DHEAS at its physiological plasma concentration may be converted into estrogens and estrogen-like compounds in breast cancer cells. The estrogenic action of DHEAS on breast cancer cells was also measured by bioluminescence in a stably transfected human breast cancer MCF-7 cell line with a reporter gene that allowed expression of the firefly luciferase enzyme under the control of an estrogen regulatory element.

Antiproliferative, anti-aromatase, anti-17beta-HSD and antioxidant activities of lignans isolated from Myristica argentea.

Four lignans were isolated from the petrol extract of Myristica argentea mace (Myristicaceae) and their structures were elucidated by means of NMR and mass spectrometry. Although they have been previously described, NMR data are only available for threo-austrobailignan-5, which has been isolated only once, and is incomplete. Three of them, erythro-austrobailignan-6, meso-dihydroguaiaretic acid and nectandrin-B, exert an antiproliferative effect on MCF-7 cells as well as antioxidant activity on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, but not the threo-austrobailignan-5. Nectandrin-B also possesses anti-17beta-hydroxysteroid dehydrogenase and anti-aromatase activities.

Aromatase in synovial cells from postmenopausal women.

Peripheral aromatization of androgens exerts estrogenic actions in many tissues. In this study, osteoarthritis synoviocytes were examined to clarify the possible action of adrenal androgen on synovial cell. Synoviocytes from postmenopausal women are able to express aromatase mRNA. By sequence analysis, the PCR fragment (485 bp) was determined to be 100% identical to that of human placental aromatase cDNA. Moreover, this study demonstrates that adrenal androgen, androstenedione, is converted to estrone (E(1)) and estradiol (E(2)) in synoviocytes by aromatase which is positively regulated by glucocorticoids such as dexamethasone. E(2) production reduced significantly IL-6 secretion. These data provide preliminary evidence that in situ estrogen production by synoviocytes may have a role in OA susceptibility. However the role of E(2) in OA is not clear and remains to be determined.

Dose-dependent modulation of apoptosis and cyclooxygenase-2 expression in human 1547 osteosarcoma cells by NS-398, a selective cyclooxygenase-2 inhibitor.

A selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, was shown to produce an anti-proliferative and pro-apoptotic effect on different types of cell lines. We describe the presence of COX-1 and COX-2 pathways in the human osteosarcoma 1547 cell line, as well as the conflicting effects of NS-398 (10, 50 and 100 microM) on programmed cell death, PGE2 release and COX-2 expression in 1547 cells cultured under apoptotic conditions. We demonstrate a link between the effects of 10 and 100 microM NS-398 on cell apoptosis, PGE2 release, and expression of COX-2 in 1547 cells undergoing apoptosis. At 10 microM, NS-398 acted as a selective COX-2 inhibitor moderately increasing apoptosis without any effect on COX-2 expression. In contrast, at 100 microM, NS-398 induced a cell cycle slowing or arrest, strongly enhanced COX-2 expression which was associated with a high PGE2 release and a marked decrease in apoptosis. This latter property of NS-398 at 100 microM in 1547 human osteosarcoma cells is novel compared to the described NS-398 pro-apoptotic effect on other cell lines.

Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities.

Chalcones were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. In the present study, we have demonstrated for the first time that chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities: these enzymes being considered as important targets in the metabolic pathways of human mammary hormone-dependent cells. Our results showed that naringenin chalcone and 4-hydroxychalcone were the most effective aromatase and 17beta-hydroxysteroid dehydrogenase inhibitors with IC50 values of 2.6 and 16 microM respectively. In addition, inhibitory effects of some flavones and flavanones were compared to those of the corresponding chalcones. A structure-activity relationship was established and regions or/and substituents essential for these inhibitory activities were determined.

Chalcones: structural requirements for antioxidant, estrogenic and antiproliferative activities.

Flavonoids are largely studied for their biological properties and particularly for their scavenging and antioxidant activities. In the present study, we first evaluated the antioxidant and the estrogenic actions of chalcones, then we tested their effects on MCF-7 cell proliferation. Chalcones are unique in the flavonoids family in lacking a heterocyclic C ring. We tested substituted chalcones with different numbers and different positions of the hydroxy groups: 2'-hydroxychalcone, 4'-hydroxychalcone, 4-hydroxychalcone, 2',4-dihydroxychalcone, isoliquiritigenin, 2',4'-dihydroxychalcone, phloretin and naringenin chalcone. For the antioxidant tests we established the importance of the alpha-beta double bond and the 6'-hydroxy group. The establishment of the structure-activity relationship for the estrogenic properties showed a correlation between the antioxidant and the estrogenic properties. The importance of conformation and hydroxy group positions observed for chalcones, having antioxidant and estrogenic properties, was also observed on MCF-7 cell growth with the same structure-activity relationship. The role of electron and hydrogen transfer in the correlation between these three biological activities was discussed.

Effects of pinostrobin on estrogen metabolism and estrogen receptor transactivation.

The interaction between the estrogen receptor and 5-hydroxy-7-methoxyflavanone (pinostrobin) was studied in the presence or absence of estradiol or dehydroepiandrosterone sulfate (DHEAS), respectively, using a stably transfected human breast cancer cell line (MVLN). We also evaluated its action on the proliferation in estrogen-dependent (MCF-7) human breast cancer cells in the same conditions than the estrogen receptor assay. On the other hand pinostrobin was evaluated for their effects on the human placental aromatase, 3beta-hydroxysteroid dehydrogenase Delta(4)/Delta(5) isomerase and 17beta-hydroxysteroid dehydrogenase activities. Pinostrobin did not possess antiestrogenic activity but presented anti-aromatase activity and decreased the growth of MCF-7 cells induced by DHEAS and E(2). This study provides particularly evidence of the potential biological interest of pinostrobin among the flavonoids.

Estrogenic/antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol.

Resveratrol, natural compound found in grapes and wine, has been reported to have a variety of health benefit properties. Based on the structural similarity to the synthetic estrogen diethylstilbestrol, we investigated estrogenic/antiestrogenic effects on human breast cancer cell lines, MCF-7 and MVLN, and scavenging properties using DPPH of both (E)- and (Z)-isomers. Both isomers increased the in vitro growth of MCF-7 cell lines at medium concentrations (10 and 25 microM) whereas the low concentrations (0.1 and 1 microM) had no effect and the high concentration (50 microM) decreased the cell growth and was cytotoxic. The 25 microM (E)-isomer alone was able to reduced the proliferation induced by the estradiol. Low concentrations of (E)- and (Z)-resveratrol (0.1 and 1 microM) and medium concentration 10 microM (Z)-resveratrol did not interfere with the estrogen receptor. In contrast, medium concentrations of (E)-resveratrol (10 and 25 microM) and (Z)-resveratrol (25 microM) functioned as superagonists of estradiol. Whatever the model used, MCF-7 or MVLN cell lines, (Z)-resveratrol was less effective than (E)-resveratrol. Extinction of DPPH and Fe(III) reduction experiments showed that both isomers of resveratrol could act as free radicals scavengers or pro-oxidant compounds. The properties of low concentrations of resveratrol raise the possibility that structure-function studies could lead to the development of more selective estrogen receptor agonists and antagonists, which could be useful as a therapeutic agent.

Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells.

Isoflavones and others phytoestrogens have been suggested to be anticarcinogenic. Anti-aromatase, antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. In this study, we explored some mechanisms by which they can exert cancer-preventive effects. Phytoestrogens were tested for estimating anti-aromatase, anti-3beta-hydroxysteroid dehydrogenase delta5/delta4 isomerase (3beta-HSD) and anti-17beta-hydroxysteroid dehydrogenase (17beta-HSD) activities in human placental microsomes. We found that isoflavonoids and compounds which presented the phenolic B ring in the 3 position on the pyran ring preferentially inhibited 3beta-HSD and/or 17beta-HSD activities than aromatase activity. We also evaluated their interactions with the estrogen receptor using a stably transfected human breast cancer cell line (MVLN). On the other hand phytoestrogens were evaluated for their effects on the proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions or/and substituents essential for these different activities. However, at high concentrations it seems that some phytoestrogens exert their protection against breast cancer through other estrogen-independent mechanisms.

C19 steroids estrogenic activity in human breast cancer cell lines: importance of dehydroepiandrosterone sulfate at physiological plasma concentration.

The estrogenic action of C19 steroids on breast cancer cells was measured by bioluminescence in stably transfected human breast cancer MCF-7 and T47D cell lines with a reporter gene that allows expression of the firefly luciferase enzyme under control of an estrogen regulatory element. The "estrogenic activity" of C19 steroids, such as dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), androst-5-en-3 beta,17 beta-diol, androst-4-en-3,17-dione, dihydrotestosterone, testosterone, and 5 alpha-androstan-3 beta,17 beta-diol was studied. This showed that DHEAS, at concentration observed in physiological conditions (10(-6) M), had a high "estrogen-like effect" in MCF-7 and T47D cell lines. Other C19 steroids, at physiological plasma concentration, alone or together did not have any significant effect on the luciferase activity. Moreover aminoglutethimide, an inhibitor of the aromatase enzyme, in the presence of C19 steroids, partially decreased the luciferase activity. These results suggest that MCF-7 and T47D cell lines could convert DHEAS to estrogen-like compounds by different enzymatic systems.

Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids.

The interaction between the estrogen receptor and a variety of flavonoids was studied in the presence or absence of estradiol using a stably-transfected human breast cancer cell line (MVLN). On the other hand, flavonoids were evaluated for their effects on proliferation in estrogen-dependent (MCF-7) and independent (MDA-MB231) human breast cancer cells. We established a relationship structure-activity and determined regions and/or substituents essential for estrogenic or antiestrogenic activities. In contrast, we did not find the same relationship for cell proliferation. Among all flavonoids used, only 7-methoxyflavanone and 7,8-dihydroxyflavone at high concentrations (50 microM) possess antiestrogenic and antiproliferative activities. These results suggest that two hydroxyls (in positions 7 and 8) or 7-methoxy substituents are essential for the antiestrogenic activity of flavonoids. However, it seems that flavonoids at high concentrations exert their antiproliferative activity through other estrogen receptor-independent mechanisms.

Dehydroepiandrosterone sulfate estrogenic action at its physiological plasma concentration in human breast cancer cell lines.

Estrogen receptor activation in hormone dependent cells (MCF-7 and T47D) and hormone independent cells (MDA-MB-231) was measured by bioluminescence in stably transfected human breast cancer MCF-7, T47D and MDA-MB-231 cell lines with a reporter gene which allows expression of the firefly luciferase enzyme under the control of an estrogen regulatory element. Estrogen receptor activation by estrogens and steroid sulfates such as estrone 3-sulfate (E1S), estradiol 3-sulfate (E2S), estriol 3-sulfate (E3S) and dehydroepiandrosterone sulfate (DHEAS) were studied and compared in these cell lines. DHEAS, at a physiological plasma concentration only (1 microM), had a high "estrogen-like" effect in MCF-7 and T47D cells. In contrast, estrogen sulfates did not have any effect on the luciferase activity at their physiological plasma concentration. These results suggest that MCF-7 and T47D cells could convert DHEAS to estrogens by aromatase and/or to estrogen-like compounds by other enzymatic systems. This is the first demonstrahon of the steroid sulfates action through their metabolites on the estrogen receptor. Therefore, at the concentrations observed in physiological conditions, DHEAS could contribute to the pool of compounds having estrogenic activities in human breast cancer hormone dependent cell lines.

Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids.

A method for estimating in the same assay both aromatase and 17beta-hydroxysteroid dehydrogenase activities in human placental microsomes using radiolabelled [1,2,6,7-3H]4-androstene-3,17-dione was proposed. In this assay, estrone (E1) and estradiol (E2) produced were separated by HPLC and estimated using a radioactive flow detector. Using this method, the inhibitory effect of various flavonoids, including flavone, flavanone and isoflavone, on the human placental aromatase and 17beta-hydroxysteroid dehydrogenase was studied. Flavonoids were shown to be potent inhibitors of both aromatase and 17beta-hydroxysteroid dehydrogenase activities. We found that 7-hydroxyflavone and apigenin are the most effective aromatase and 17beta-hydroxysteroid dehydrogenase inhibitors, respectively. Experiments showed that a hydroxyl group in position 7 was essential for anti-17beta-hydroxysteroid dehydrogenase activity. However, flavonoids with 7-methoxy or 8-hydroxyl groups on the A ring showed only anti-aromatase activity. Structure-activity relationships were discussed.