Effect of chronic administration of vitamin E on the hemopoietic system in hypercholesterolemia

Hypercholesterolemia induces oxidative stress, which is known to have adverse effects on the integrity of cells. Hence, hypercholesterolemia may have adverse effects on the hemopoietic system. Vitamin E, an antioxidant, is being used by normo- and hypercholesterolemic subjects. It is, however, not known if vitamin E has any beneficial or adverse effects on the hemopoietic system. The objectives of this study are to determine if (i) hypercholesterolemia has any adverse effects on the hemopoietic system [red blood cell (RBC) count, mean corpuscular volume (MCV), red blood cell distribution width (RDW), hematocrit (Hct), hemoglobin (Hb), mean corpuscular hemoglobin (MCH), MCH concentration (MCHC), white blood cell (WBC), and platelet counts, and mean platelet volume (MPV)], and (ii) vitamin E has any effect on the hemopoietic system in hypercholesterolemia. Blood samples were collected before and at various intervals during a high cholesterol diet (0.25% cholesterol) for 2 and 4 months, and while on high cholesterol diet with vitamin E (2 months) following a high cholesterol diet (2 months). Serum cholesterol was measured on an automated Clinical System Analyzer and hemopoietic parameters were measured on an automated Cell-dyn-4000. The results show that hypercholesterolemia decreased RBC count, Hct and Hb, increased MCV, RDW, MCH, and MCHC, and had no effect on WBC and platelet counts, and MPV. Vitamin E did not affect any of the parameters of the hemopoietic system. In conclusion, hypercholesterolemia of short duration has adverse effects on certain elements of the hemopoietic system. Vitamin E does not affect the hemopoietic system during hypercholesterolemia.     

Mature hematology in neonatal walruses supports diving alongside their mothers

An animal's physiology limits the environmental conditions where it can persist; quantifying the physiology of the walrus is timely since they are being impacted by alterations in sea ice. We examined postnatal changes in hematology, an important attribute that supports diving, by analyzing a longitudinal data set from aquaria walruses (five males and nine females) sampled from 0.04 to 12.0 years of age (n = 795 samples). Red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean cell hemoglobin (MCH), and mean corpuscular hemoglobin content (MCHC) did not change markedly after birth and appears to have not been influenced by sex. Estimated values at birth were RBC: 3.78 ± 0.12 × 10⁶ mm⁻³, Hb: 17.62 ± 0.82 g dl⁻¹, Hct: 45.21 ± 2.01%, MCV: 118.99 ± 3.99 fl, MCH: 47.10 ± 1.77 pg, and MCHC: 39.60 ± 0.70 g dl⁻¹. Compared to newborns, there were only subtle decreases in RBC, Hb, and MCHC, and a slight increase in MCV in the years following birth; Hct and MCH appear not to have changed. Unlike other pinnipeds, walruses swim within days of birth and have a prolonged 2-year nursing interval. Mature hematology early in life supports breath-holding, as young walruses must transit under sea ice with patchily distributed breathing holes.     

猪2、7和8号染色体上影响血常规指标的数量性状基因座(QTL)检测

以3个品种（长白猪、大白猪、松辽黑猪）16个公猪家系共计368头仔猪组成资源群体,在猪2、7和8号染色体上共选取35个微卫星标记,采用基于线性混合模型的方差组分分析方法,对影响与猪白细胞、红细胞和血小板相关的共计18项血常规指标的数量性状基因座（quantitative trait loci,QTL）进行了检测．通过似然比检验,并以自由度为2的卡方分布作为检验统计量的分布,共发现22个在P〈5％水平下显著的QTL,其中在2号染色体上有9个,分别影响白细胞总数、中性粒细胞数、平均红细胞体积、血红蛋白含量、平均红细胞血红蛋白浓度、血小板总数、平均血小板体积、血小板分布宽度和血小板压积,在7号染色体有7个,分别影响白细胞总数、中性粒细胞数、平均红细胞血红蛋白浓度、血红蛋白含量、血小板总数、平均红细胞体积和红细胞分布宽度变异,在8号染色体上有6个,分别影响中性粒细胞百分比、淋巴细胞百分比、平均红细胞血红蛋白浓度、血小板总数、血小板压积和平均红细胞体积．为尽可能地避免由于多重检验所造成的假阳性率的升高,我们采用了控制假检出率（false discovery rate,FDR）的方法来对这22个QTL进行进一步检验,发现有14个达到FDR〈5％显著水平,其中又有9个达到FDR〈1％显著水平．     

Lack of prominent compensatory polycythemia in traditional native Andeans living at 4,200 meters

Red blood cell count (RBC), hemoglobin concentration ([Hb]) and hematocrit (Hct) were measured in 303 male Quechua children and adults, aged 6 to 57 years, living a lifestyle as traditional pastoralists and horticulturalists at a mean altitude of 4,200 m in the Southern Peruvian Andes. Values for RBC, [Hb], and Hct increased with age from middle childhood to young adulthood. However, among adults there was no significant association between age and any of these three parameters. Overall, there was approximately a 10-12% increase in the RBC, [Hb], and Hct above sea-level norms for all age groups. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) showed a slight but significant increase with age in children and adolescents, but the mean corpuscular hemoglobin concentration (MCHC) did not. We conclude that the study of highland Quechua Indians, living a traditional lifestyle as pastoralists and horticulturalists, does not support the long-held belief that altitude hypoxia provokes a dramatic compensatory polycythemia in healthy Andeans.     

Changes in hematological parameters in free-living pigeons (Columba livia f. urbana) during the breeding cycle

The blood parameters—red blood cell (RBC) count, hematocrit (Ht), hemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)—were studied for the first time in free ranging pigeons Columba livia f. urbana. The aim of the study was to establish a set of reference values for this ubiquitous urban species and to examine a potential influence of the factors such as sex and phase of the breeding cycle on the hematological parameters. Blood was sampled from the adult individuals of both sexes during the breeding cycle. Significant variations in Ht and Hb were observed, while RBC count remained unchanged. The lower hematocrit value and hemoglobin concentration found in both males and females during molt probably resulted from the increase of plasma volume not accompanied by an increase in RBC. On the other hand, a significant physiological stress of nutritional deficiency during this energy-consuming stage may manifest itself in the decreased Ht and Hb values. The higher values of Ht and Hb during the laying phase could be related to the dehydration status. There were no overall differences in MCV, MCH, and MCHC values in either of the breeding stage. A lack of sex dimorphism in the measured and calculated blood parameters was apparent. Data collected herein contribute to the better understanding of general physiology of the ubiquitous urban species. The knowledge of variation in the blood indexes with respect to sex and breeding stage is crucial before blood parameters can provide an useful information on physical condition of the bird.     

Age and gender related changes in hematological parameters of thoroughbred foals

Abstract

Hematological and biochemical profiles commonly are required in equine medicine. We studied hematological parameters including red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), hematocrit (PCV), differential leukocyte counts, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in thoroughbred foals at different ages and for both sexes. Sixty healthy thoroughbred foals, 1 day, 3 days and 1 year old were used. Each age group consisted of 10 male and 10 female animals. We found significant differences related to age in RBC values of females, PCV, MCV values of males, WBC, neutrophil percentages, lymphocyte percentages, monocyte percentages of females, and eosinophil percentages and basophil percentages. Significant differences related to gender were found only with regard to PCV at 1 year and WBC at 1 day. The hematological parameters of thoroughbred foals up to one year old may be useful for evaluating and monitoring the health of these animals.     

The effects of L-carnitine on some hematological parameters in rats fed a cholesterol-rich diet

We evaluated the effects of L-carnitine on the hematological characteristics of rats fed a cholesterol-rich diet. Healthy male Wistar Albino rats were assigned to four equal groups. During the 40 day experiment, group 1 was fed standard rat pellets, group 2 was fed standard rat pellets containing 7.5 % cholesterol powder, group 3 was fed standard rat pellets and water that contained 75 mg/l L-carnitine, and group 4 was fed standard rat pellets that contained 7.5% cholesterol and water that contained 75 mg/l L-carnitine. Blood samples were analyzed for red (RBC) and white (WBC) blood cells, hemoglobin, hematocrit, granulocytes, lymphocytes, monocytes, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) using an automated cell counter. The RBC count in the group that received the 7.5% cholesterol diet was decreased significantly compared to the other groups. The hematocrit of the cholesterol group was lower than for the L-carnitine + cholesterol and L-carnitine groups. The MCV in the cholesterol group was significantly higher than the control group. The MCH in the cholesterol group was higher than for the other groups. There was no significant difference among the groups with regard to hemoglobin, MCHC, WBCs and leukocyte types. L-carnitine appears to have beneficial effects on erythrocyte stability, erythropoiesis and hyperlipidemia.     

Hematological responses to thermal acclimation in a cold water squaliform (Heterodontus francisci girard)

Summary The hematological modifications occurring as a result of acclimation to increased temperature in the cold water horn shark,Heterodontus francisci, were evaluated. Sharks were maintained under constant conditions except for temperature (15°C and 25°C) in a closed marine system. The total red blood cell (RBC) number decreased in the 25°C sharks. In contrast, hemoglobin concentration, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) significantly increased at 25°C compared to the control animals. RBC size was increased at 25°C, but the surface area/mm³ whole blood was reduced. Folic acid levels were not different between the groups. Vitamin B₁₂ levels decreased and testosterone increased at 25°C. Blood pH, number of erythroblasts, number of white blood cells (WBC) and WBC differential analyses were essentially unchanged at the two temperatures, except that the relative neutrophil number was increased. The major hematological changes occur in the erythrocytes and appear to be sequential in nature with an initial loss of RBC followed by increased hemoglobin synthesis and increased RBC size, but lack of recovery of RBC numbers.Abbreviations Hb hemoglobin - Hct hematocrit - MCH(C) mean corpuscular hemoglobin (concentration) - MCV mean corpuscular volume - RBC red blood cells - WBC white blood cells Contribution Number 359, Department of Biology     

Quantitative trait loci for porcine baseline erythroid traits at three growth ages in a White Duroc × Erhualian F<Subscript>2</Subscript> resource population

Baseline erythroid indices are increasingly involved as risk factors for common complex diseases in humans. However, little is known about the genetic architecture of baseline erythroid traits in pigs. In this study, hematocrit (Hct), hemoglobin (Hgb), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell (RBC), and red cell distribution width (RDW) were measured in 1420 (day 18), 1410 (day 46), and 1033 (day 240) F(2) pigs from a White Duroc x Erhualian intercross resource population. The entire resource population was genotyped for 183 microsatellite loci across the pig genome, and the quantitative trait loci (QTL) analysis was performed for all erythroid-related traits measured with QTL Express based on a least-squares method. A total of 101 QTL, including 46 genome-wide significant QTL and 55 chromosome-wide significant QTL, regulating erythroid traits were found on all pig chromosomes (SSC) except for SSC15 and SSC18. The genome-wide significant QTL were mainly localized on SSC1, 7, 8, 10, and X. These results confirmed most of QTL previously identified in the swine. More importantly, this study detected age-specific QTL for baseline erythroid traits in pigs for the first time. Notably, the QTL for MCV and MCH on day 18 on SSC8 with small intervals of 3 and 4 cM, respectively, provided a good starting point for identifying causal genes underlying MCV and MCH in the future.     

Development of hematological respiratory variables in late chicken embryos: the relative importance of incubation time and embryo mass

Oxygen demand increases during embryonic development, requiring an increase in red blood cells (RBCs) containing hemoglobin (Hb) to transport O(2) between the respiratory organ and systemic tissues. A thorough ontogenetic understanding of the onset and maturation of the complex regulatory processes for RBC concentration ([RBC]), Hb concentration ([Hb]), hematocrit (Hct), mean corpuscular indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration ([MCHb])) is currently lacking. We hypothesize that during the last half of incubation when the respiratory organ (the chorioallantoic membrane) envelops most of the egg contents, mean corpuscular indices will stabilize. Accordingly, Hct, [RBC] and [Hb] must also all change proportionally across development. Further, we hypothesize that the hematological respiratory variables develop and mature as a function of incubation duration, independently of embryonic growth. As predicted, a similar increase in Hct (from 18.7±0.6% on day 10 (d10) to 34.1±0.5% on d19 of incubation), [RBC] (1.13±0.03×10(6)/μL to 2.50±0.03×10(6)/μL) and [Hb] (6.1±0.2 g% to 11.2±0.1 g%) occurred during d10-19. Both [RBC] and [Hb] demonstrated high linear correlation with Hct, resulting in constant [MCHb] (~33 g% from d10 to d19). The decrease in MCV (from ~165 μ(3) on d10 to ~140 μ(3) on d13) and MCH (~55 pg to ~45 pg) during d10-13, may be attributed to a changeover from larger primary to smaller secondary and adult-type erythrocytes with MCV and MCH remaining constant (~140 μ(3) and ~45 pg respectively) for the rest of the incubation period (d13-19). Hematological respiratory values on a given incubation day were identical between embryos of different masses using either natural mass variation or experimental growth acceleration, indicating that the hematological variables develop as a function of incubation time, irrespective of embryo growth.     

Effect in vivo of atrazine on haematology and O2 consumption in fish, Tilapia mossambica.

Studies were conducted on haematological constituents such as Red blood cells (RBC), White blood cells (WBC), Haemoglobin (Hb), Packed cell volume (PCV), Mean cell volume (MCV), Mean corpuscular haemoglobin (MCH), Mean corpuscular haemoglobin concentration (MCHC), Blood volume (BV), Blood water content (BWC) and Whole animal oxygen consumption (WAOC) in the fish exposed to sublethal concentration of atrazine. Significant changes were seen in the constituents of the blood and O2 consumption of fish suggesting the existence of respiratory distress in the fish as a consequence of atrazine toxicity.     

The effect of different dietary iron levels on growth and hepatic iron concentration in juvenile gibel carp (Carassius auratus gibelio)

An 83-day growth trial was conducted using a flow-through system to examine the effects of different dietary iron levels on growth and hepatic iron concentration in juvenile gibel carp ( Carassius auratus gibelio ). Six purified diets supplemented with different levels of iron (0, 10, 30, 60, 100 and 200 mg kg⁻¹) (as ferrous sulfate) were fed to triplicate groups of fish (initial weight 2.12 ± 0.00 g per fish). The results showed that the addition of iron to the basal diet did not significantly affect the specific growth rate (SGR), feed efficiency (FE), survival, red blood cell amount (RBC), hemoglobin content (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) or mean corpuscular hemoglobin concentration (MCHC). Hepatic iron concentration and hematocrit (Hct) were significantly influenced by dietary iron level (P < 0.05). On the basis of the iron concentration for the maintenance of optimum hepatic iron concentration and Hct, it was concluded that the dietary iron concentration of juvenile gibel carp should be not less than 202 mg Fe kg⁻¹ diet.     

甘肃鼢鼠血象及其与低氧适应的关系

甘肃鼢鼠(Myospalax cansus)是一种严格营地下生活的鼠类,其形态、行为及生理特征均与地面鼠不同。为探讨甘肃鼢鼠适应低氧环境的机理,本研究采用血象指标测定方法,对甘肃鼢鼠低氧适应前后的红细胞数、血红蛋白浓度、红细胞压积等各血象指标进行测定。结果显示,甘肃鼢鼠低氧适应后红细胞数、血红蛋白浓度和红细胞压积均显著升高,而平均红细胞体积、平均红细胞血红蛋白及平均红细胞血红蛋白浓度明显下降。与地面生活的啮齿动物低氧适应后血象相比,甘肃鼢鼠红细胞数量多,红细胞压积大,血红蛋白浓度高,红细胞膜表面积大,血红蛋白的利用率较高,可能是对低氧环境适应的一种途径。     

Effect of storage time on haematological parameters in mullet,Mugil cephalus

The aim of the present study was to assess the effect of storage time at +4 °C on red blood cell count (RBC), haematocrit (Hct), haemoglobin (Hb), white blood cell count (WBC), thrombocyte count (TC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) in mullet (Mugil cephalus) using an automatic method. After blood collection (T₀), all samples were analyzed using both the manual and automatic method. To test the validation of the automatic method, a paired t‐test was applied, and no statistical difference was observed. The samples were successively divided into four different aliquots and stored at +4 °C to assess the haematological parameters using the automatic method. The first aliquot was refrigerated for 6 h, the second one for 24 h, the third one for 48 h and the last one at for 72 h. One‐way repeated‐measures ANOVA showed a significant effect of storage time (P < 0.05) on Hb, WBC, TC, MCH and MCHC. These results suggest that haematological parameters can be assessed within 6 h from blood collection when samples are stored at +4 °C because long‐term storage modifies the results of the analyses. Further studies on these parameters could be still needed in various fish species to validate an appropriate method for haematological analysis useful not only for the evaluation of the health status of animal living in captivity and in aquaculture but also to have reliability environmental haematological biomarkers. Copyright © 2012 John Wiley & Sons, Ltd.     

Haematological studies on the prewintering and wintering frog, Rana esculenta

1. A study of the haematology of the frog Rana esculenta including erythrocyte count (RBC), haemoglobin content (Hb), haematocrit (HCT), mean cell volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and erythrocyte size as a function of prewinter and winter was made. 2. The RBC count and Hb were significantly higher in contrast to MCV and MCH values during prewinter in both sexes. 3. The surface area to volume ratio was higher in prewinter whereas the length to width ratio (eccentricity) of the cytosome and nucleus was significantly higher during winter in both sexes. 4. Sexual differences in the erythrocyte count, Hb content and the surface area to volume ratio were also observed. 5. The physiological significance of these observations are reported for Rana esculenta.     

Toxicity bioassay in Sprague-Dawley rats exposed to 20 kHz triangular magnetic field for 90 days

Sprague-Dawley rats (10 each of male and female per group for sham and magnetic field exposed) were exposed in a carrousel irradiator to 20 kHz intermediate frequency (IF) magnetic field at 6.25 microT rms for 8 h/day, 5 days/week for 90 days. Urine analysis (pH, serum glucose, protein, ketone bodies, RBC, WBC, bilirubin, urobilinogen, and specific gravity), blood analysis [WBC, RBC, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thrombocyte count, and leucocyte count], blood biochemistry (total protein, blood urea nitrogen, creatinine, glucose, total bilirubin, total cholesterol, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase), and histopathological analysis for organs such as liver, kidney, testis, ovary, spleen, brain, heart, and lung were performed on day 90. Results showed no significant differences in the above analyses between IF magnetic field exposed and sham control rats. Therefore, we conclude that there were no significant toxicities in rats exposed to 20 kHz IF triangular magnetic field-exposure for 90 days.     

Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters

Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animals exhibiting altered values and transmission of the phenotypic deviations to the subsequent generations led to the successful establishment of mutant lines for the parameters MCV, RBC, and PLT. Analysis of the causative mutation was started in selected lines, thereby revealing a novel mutation in the transferrin receptor gene (Tfrc) in one line. Thus, novel phenotype-driven mouse models were established to analyze the genetic components of hematological disorders.     

Haematological profile of common carp spawners of various breeds

The goal of this study was to determine the basic haematological profile of common carp (Cyprinus carpio L.) spawners of eight breeds reared under identical conditions and sampled in spring after overwintering. Significant differences were found among the breeds for haemoglobin level (Hb), haematocrit value (PCV), mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) values. The number of red blood cells (RBC), mean corpuscular haemoglobin concentration (MCHC), number of leukocytes (WBC) and leukocyte differential count (WBC DIFF) did not differ significantly among the respective breeds. The highest Hb, PCV and MCH values were found for Ropsha scaly carp (ROP) and Amur wild carp (AS) (Hb 109 ± 17 and 106 ± 15 g l^?1; PCV 0.40 ± 0.06 and 0.40 ± 0.06 l l^?1; MCH 69 ± 7 and 69 ± 9 pg, respectively). The AS specimens and breeds that originated [ROP, Ukraine scaly carp (US), and Northern mirror carp (M72)] showed significantly higher values of Hb (P < 0.01), PCV (P < 0.01), MCV (P < 0.05) and MCH (P < 0.05), compared to the other four breeds: Hungarian mirror carp (M2), Israeli mirror carp (Dor 70), South Bohemian mirror carp (BV) and Tata scaly carp (TAT). Males showed significantly higher PCV, Hb and RBC values within individual breeds. This study demonstrated that Amur wild carp and breeds originating from it had significantly higher values of erythrocyte profile in comparison with the other breeds studied.     

Effects of confinement stress and additional zinc treatment on some blood parameters in the dogfish Scyliorhinus canicula

Several blood parameters were studied in the dogfish Scyliorhinus canicula subjected to different confinement conditions (transport and maintenance) and zinc contamination. Confinement stress significantly decreased erythrocyte counts (RBCC), haematocrit (Ht), haemoglobin (Hb), leucocrit (Lt), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). Mean corpuscular volume (MCV) did not change with this stress and plasma glucose concentration significantly increased. In fish subjected to confinement stress conditions, Zn treatment significantly decreased Hb, MCH and MCHC and plasma glucose concentration. Ht and MCV did not change and Lt and RBCC significantly increased. Results are discussed related to other stress effects and effects of zinc treatment on fish confined in non-stressful conditions.     

Testosterone action on erythropoiesis does not require its aromatization to estrogen: Insights from the testosterone and estrogen treatment of two aromatase-deficient men

Androgens act on erythropoiesis, but the relative role of testosterone (T) and estradiol (E₂) on erythropoietic parameters in men is a poorly investigated issue. In order to evaluate separately the effects on erythropoiesis of high-dose T administration alone and of physiological dose of E₂ administration alone two adult men with aromatase deficiency were assessed before and during each treatment. Blood cell count, hemoglobin (Hb), hematocrit (Hct), erythrocyte mean cell volume (MCV), erythrocyte mean corpuscular hemoglobin (MCH), erythrocyte mean corpuscular hemoglobin concentration (MCHC), serum ferritin, iron and total iron-binding capacity (TIBC), serum erythropoietin, serum total testosterone and estradiol were evaluated. Hb, Hct and red cell count rose during testosterone treatment, consistently with the increase in circulating testosterone, but failed to increase during estradiol treatment. A decrease in Hb, Hct and red cell count was recorded in one of the two subjects during estradiol treatment, with a concomitant decrease in serum testosterone. Circulating T alone is capable of and sufficient to influence erythropoiesis, especially at supraphysiological dosage, while circulating E₂ have not the same effect on erythropoietic parameters, suggesting the hypothesis that the erythropoietic changes induced by androgens are not mediated via its aromatization to estrogens.