Biotransformation and bioconcentration of steroid estrogens by Chlorella vulgaris

The biotransformation and bioconcentration of natural and synthetic steroid estrogens by Chlorella vulgaris were investigated using batch shaking experiments with incubation for 48 hours in the light or dark. Estradiol and estrone were inter-convertible in both light and dark conditions, however this biotransformation showed a preference to estrone. In the light, 50% of estradiol was further metabolized to an unknown product. Apart from biotransformation, estrone as well as hydroxyestrone, estriol and ethinylestradiol were relatively stable in the algal culture, while estradiol valerate was hydrolyzed to estradiol and then estrone within 3 hours of incubation. All the tested estrogens exhibited a degree of partitioning to C. vulgaris, however, the concentrations of estriol, hydroxyestrone, ethinylestradiol and estradiol valerate were always below the quantification limits. For estradiol and estrone, the partitioning of these estrogens in the algal extracts to the filtrates was below 6% of the total present. The average concentration factor for estrone was around 27, however the concentration factor for estradiol is not reported since no equilibrium was reached between aqueous solution and that within the cells due to continuing biotransformation

A new method for the separation of androgens from estrogens and for the partition of estriol from the estrone-estradiol fraction: with special reference to the identification and quantitative microdetermination of estrogens by ultraviolet absorption spectrophotometry

It is recognized generally that a qualitative and quantitative knowledge of the excretion pattern of the urinary estrogens is one index to an understanding of the functional activity of the ovary and adrenal cortex. Obviously, such determinations may be useful also in evaluating the normal and abnormal functions of other physiologically related endocrine glands as well as of organs like the liver and kidneys. The clinical applications of these data are self-evident. Various attempts have been made to circumvent the notoriously inaccurate values which have been obtained for the urinary estrogens by a variety of bioassay methods and calorimetric techniques (1, 2). The acknowledged shortcomings of these methods have led us to investigate the application of ultraviolet absorption spectrophotometry to the quantitative determination of the urinary estrogens in an attempt to develop an objective physical method for their accurate determination. It is known that the infra-red portion of the spectrum yields more differentially characteristic curves, but those of the ultraviolet range are more readily obtainable, and consequently better adapted to clinical use. This communication is concerned with studies of the following aspects of the problem: (1) spectrophotometric identification and quantitative micro determination of crystalline estrogens; (2) detection by spectrophotometric assay of gross errors in current methods for extraction and partition of estrogens; (3) studies on the ultraviolet absorption of substances comprising the background material; (4) separation of the phenolic estrogens from the so called neutral steroid fraction; (5) separation of urinary estrogens from other urinary phenolic substances by steam distillation; (6) micro-Girard separation of estrone from estradiol; (7) an essentially new method for the extraction and partition of crystalline estrone, estradiol, and estriol, and their quantitative assay by ultraviolet spectrophotometry

Sex hormones in allergic conjunctivitis: altered levels of circulating androgens and estrogens in children and adolescents with vernal keratoconjunctivitis

PURPOSE: Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. METHODS: 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. RESULTS: Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). CONCLUSIONS AND RELEVANCE: VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC

Structure of Equilenin at 100 K: an estrone-related steroid

The structure of the estrone-related steroid, Equilenin, C18H18O2 (systematic name 3-hy-droxy-13-methyl-11,12,13,14,15,16-hexa-hydro-cyclo-penta-[a]phen-anthren-17-one), has been determined at 100 K. The crystals are ortho-rhom-bic, P212121, and the absolute structure of the mol-ecule in the crystal has been determined by resonant scattering [Flack parameter = -0.05 (4)]. The C atoms of the A and B rings are almost coplanar, with an r.m.s. deviation from planarity of 0.0104 Å. The C ring has a sofa conformation, while the D ring has an envelope conformation with the methine C atom as the flap. The keto O atom and the methyl group are translated 0.78 and 0.79 Å, respectively, from the equivalent positions on 17β-estrone. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains parallel to the c-axis direction

Cysteine-10 on 17 β-Hydroxysteroid dehydrogenase 1 has stabilizing interactions in the cofactor binding region and renders sensitivity to sulfhydryl modifying chemicals

17 β-Hydroxysteroid dehydrogenase type 1 (17 β -HSD1) catalyzes the conversion of estrone to the potent estrogen estradiol. 17 β -HSD1 is highly expressed in breast and ovary tissues and represents a prognostic marker for the tumor progression and survival of patients with breast cancer and other estrogen-dependent tumors. Therefore, the enzyme is considered a promising drug target against estrogen-dependent cancers. For the development of novel inhibitors, an improved understanding of the structure-function relationships is essential. In the present study, we examined the role of a cysteine residue, Cys(10), in the Rossmann-fold NADPH binding region, for 17 β -HSD1 function and tested the sensitivity towards sulfhydryl modifying chemicals. 3D structure modeling revealed important interactions of Cys(10) with residues involved in the stabilization of amino acids of the NADPH binding pocket. Analysis of enzyme activity revealed that 17 β -HSD1 was irreversibly inhibited by the sulfhydryl modifying agents N-ethylmaleimide (NEM) and dithiocarbamates. Preincubation with increasing concentrations of NADPH protected 17 β -HSD1 from inhibition by these chemicals. Cys(10)Ser mutant 17 β -HSD1 was partially protected from inhibition by NEM and dithiocarbamates, emphasizing the importance of Cys(10) in the cofactor binding region. Substitution of Cys(10) with serine resulted in a decreased protein half-life, without significantly altering kinetic properties. Despite the fact that Cys(10) on 17 β -HSD1 seems to have limited potential as a target for new enzyme inhibitors, the present study provides new insight into the structure-function relationships of this enzyme

Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and cytostatic activity

A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride. All of the derivatives with acetoxy groups in positions 3 and 10 bind to the estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6 (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group. Introduction of additional oxygen functions in the 2- and/or 11-position decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6-ethyl (6c) derivatives revealed that the receptor binding is mainly due to one optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7 breast cancer cells, compounds with one acetoxy group in each aromatic ring strongly inhibited cellular growth. Despite marked differences in receptor affinity, the enantiomers displayed similar activities in this cell culture. In hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect was recorded at 10-5 M. In the immature mouse uterine weight test, minimal estrogenic activity was observed. At higher doses, a significant anti-estrogenic effect became evident. It is assumed that the estrogen antagonism is responsible for the specific cytostatic effect in MCF-7 breast cancer cells

Biological variables in forager fertility performance: a critique of Bongaarts' model

African Studies Center Working Paper No. 60During the period of the 1960s and 1970s, a considerable amount of scholarly energy was devoted to studying the process of "modernization." Scholars, particularly political scientists and anthropologists, theorized extensively over exactly what modernization was and debated how it could best be quantified and measured.1 By the 1980s, however, the very notion of the "modern," along with its antithesis, the "traditional" was falling out of favor. Indeed, by declaring the new era "post-modern," the academic avant-guard signaled that the concept of modernity had effectively been relegated to the past. The past, however, is the turf of historians, so perhaps now that the concept of modernity has become old-fashioned it is time for historians to take their turn at examining its meaning. This paper will approach the concept of the "modern" by examining the role of advertising in creating notions of modernity in independence-era Ghana. Ghana, at the time of independence in 1957, was a country of supreme optimism about the future. Not only did Ghanaians see themselves as being on the cutting edge politically (as the first sub-Saharan colony to achieve independence), but they also believed that independence would bring a new era of economic development and wealth. Ghana, as a country, was "going places." The new nation's optimism found many manifestations, but this paper will focus on only one aspect of this exuberance—representations of transportation as modernity in the advertisements and articles of Ghana's premier newspaper, the Daily Graphic. As stated before, early scholarship on modernization was concerned primarily with developing a way of measuring the demise of the traditional and the rise of the modern. Such studies focused on examining populations of "traditional" or "transitional" peoples to attempt to discern just how "modern" they had or had not become. What the previous studies did not consider, and what this paper seeks to examine, is exactly how modernity was presented to and by such populations. No single factor seems to represent modernity more than motion itself—be it actual movement across space or be it social and economic change. Indeed, Daniel Lerner, the prominent scholar of modernity, defined the key aspect of being modern as having... [TRUNCATED

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR

Treatment and removal strategies for estrogens from wastewater

Natural and synthetic steroidal estrogens (estrone, 17β-estradiol and 17α-ethinylestradiol) are endocrine disrupters, that are discharged consistently from the sewage treatment works into surface waters, thereby causing endocrine disrupting effects to aquatic organisms at trace concentrations (nanogram per litre). Several years of research have been focused on their fate, behaviour and removal in the environment but primarily in the sewage treatment works which acts as a sink for these compounds. This review attempts to summarize the factors involved in the removal of these chemicals from the sewage treatment works. Biological processes, and to a limited extent physio-chemical properties, play a vital role in the endocrinal deactivation of which these compounds. The efficiency of these processes is highly dependent on operating parameters (such as sludge retention time, redox potential, etc) that govern the secondary treatment process of a functional sewage treatment works. Although advanced treatment technologies are available, cost and operational considerations do not make them a sustainable solution