Plasma level of hydroxysteroid (17-ß) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fms-like tyrosine kinase 1/placental growth factor ratio.

Mean blood pressure (MBP), bilateral notching (BN) in the uterine artery and increased circulating levels of soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio are predictors of preeclampsia (PE). Recently, we disclosed that reducing the plasma level of hydroxysteroid (17-ß) dehydrogenase 1 (HSD17B1), which is a steroidogenetic enzyme catalyzing the conversion of estrone to 17ß-estradiol, is a potential prognostic factor for PE. Our aim was to evaluate whether HSD17B1 is an independent risk factor for predicting PE after adjusting for the effects of MBP, BN and the plasma level of the sFlt-1/PlGF ratio in the second trimester. One hundred and twenty-eight consecutive normal pregnant women without gestational hypertension (GH) or PE and 30 women with PE were selected from 1724 pregnant women. Multivariate logistic regression with a forward stepwise procedure was used to construct a prediction model. A past history of GH/PE, a family history of hypertension, pre-pregnancy body mass index, MBP, BN, plasma levels of sFlt-1/PlGF ratio and plasma levels of HSD17B1 were significantly associated with the occurrence of PE; however, only MBP (OR (95% confidence interval), 1.08 (1.03-1.14)), BN (7.5 (1.9-30)), sFlt-1/PlGF (21 (2.7-163)) and HSD17B1 (0.43 (0.22-0.85)) were independent risk factors for PE. The area under the receiver-operating-characteristic curve for the combination model was 0.89, yielding a sensitivity of 0.84, a specificity of 0.88 and a positive likelihood ratio of 7.2 (4.0-13). In conclusion, HSD17B1 is an independent risk factor for PE, and the combination of several risk factors including HSD17B1 in the second trimester may improve the prediction of PE.

Polymorphisms in steroidogenesis genes, sex steroid levels, and high myopia in the Taiwanese population.

PURPOSE: To evaluate the relationship among single nucleotide polymorphisms (SNPs) in steroidogenesis enzyme genes, serum levels of sex steroids, and high myopia in Taiwanese male and female populations. METHODS: A campus-based sample of 283 cases (145 males and 138 females) with high myopia and 280 controls (144 males and 136 females) with low myopia or emmetropia was studied. Estradiol, progesterone, and testosterone levels were determined using enzyme-linked immunosorbent assay kits. We genotyped six SNPs within five steroidogenesis enzyme genes (17 alpha-hydroxylase/17,20 lyase [CYP17A1], 3 beta-hydroxysteroid dehydrogenase [HSD3B1], 17 beta-hydroxysteroid dehydrogenase 1 [HSD17B1], steroid-5-alpha-reductase, alpha polypeptide 2 [SRD5A2], and aromatase [CYP19A1]) using polymerase chain reaction-restriction fragment length polymorphism methods. Student's t-tests, χ(2) tests, logistic regression, multifactor dimensionality reduction (MDR) methods, and ANOVA were used to determine significance. RESULTS: An MDR analysis corroborated the synergistic genotype association and demonstrated that synergistic interaction between rs6203 (HSD3B1), rs10046 (CYP19A1), and sex might confer susceptibility to high myopia (p=0.019). In both male and female subjects, levels of testosterone were significantly higher in cases than in controls; in male subjects, the levels of estradiol were significantly higher and those of progesterone were significantly lower in cases (all p-values <0.001). The rs605059 (HSD17B1), with sex-gene interaction, showed association with estradiol levels in males (p=0.035) and testosterone levels in females (p=0.027). CONCLUSIONS: Testosterone levels correlate with high myopia, and interaction of steroidogenesis enzyme genes and sex may be a modulating factor in sex hormone metabolism and high-myopia risk.

Effects of gender on serum biomarkers of systemic inflammation coincident to experimentally-induced periapical lesions.

OBJECTIVE: The literature suggests that females have less adverse effects to infection than males, due to the protective effects of oestrogen. The purpose of our study is to compare the systemic effects of induced periapical lesions between groups of animals with various serum concentrations of oestrogen. METHODS: To induce periapical inflammation, two molar tooth pulps were exposed in ovariectomized (OVX) and normal female (F) and castrated (Cast-M) and normal male (M) Sprague-Dawley rats (Experimental group, E). Sham-operated control animals from each group were also studied (Control group, C). Twenty-eight days later, serum and maxillas were collected. Serum 17ß-oestradiol, testosterone, MMP-9, IL-18, IL-6, TNF-α, and IL-1ß concentrations were measured by ELISA. Maxillas were cleaned of residual tissue and digital radiographs were made to verify the presence of periapical lesions. Data were compared by factorial ANOVA, post hoc Tukey, and Pearson correlation tests. Groups were considered to be significantly different when p<0.05. RESULTS: The serum concentration of IL-18, TNF-α, IL-1-ß, IL-6 and MMP-9 was greatest in OVX-E animals, compared to all other groups (p<0.001). F-E rats had significantly higher serum concentrations of these cytokines, compared to F-C. The fold difference in serum concentration of the biomarkers (between E and C groups) was significantly greater in females than males, even though males had higher baseline concentrations of all these biomarkers. CONCLUSION: When females are oestrogen-deficient, their systemic response to periapical lesions is significantly greater than males, suggesting that oestrogen is essential in protecting females from the effects of this type of inflammation.

A multiparametric analysis of endometrial estrogen and progesterone receptors after the postovulatory administration of mifepristone.

A double-blind randomized study was performed in two groups of eight normally cycling patients: group I received 10 mg/d of RU486 for 4 days from the date of ovulation and group II received a placebo. On day +5, cytosol and endometrial estrogen receptors (ERs), and progesterone receptors (PRs) were analyzed by radioligand binding assay as well as by enzyme immunochemistry. Histologic studies showed that all the endometria of group I were abnormal (luteal insufficiency and/or E/P imbalance). The nuclear PR levels were significantly higher in group I (843 +/- 422 fmol/mg) deoxyribonucleic (DNA) compared with 482 +/- 232 fmol/mg DNA in group II. Immunohistochemical study showed that ER and PR staining was higher for both glands and stroma in group I (52% and 72% for the respective receptors), compared with the receptor-immunostained surface observed in group II, which was reduced to 40% for ER and to 4% for PR. This study demonstrates that RU486 administered in the immediate postovulatory period blocks normal tissue evolution in the follicular phase as well as the processing of PR.

17 beta-Hydroxysteroid oxidoreductase: a ubiquitous enzyme. Interconversion of estrone and estradiol-17 beta in BALB/c mouse tissues.

A survey was conducted to define the sites of 17 beta-hydroxysteroid oxidoreductase activity in organs and tissues of male and female BALB/c mice, as well as the favored direction of the oxidoreductase reaction in intact tissues. The enzyme activity was assayed by use of radiolabeled estrone and estradiol-17 beta as substrates. Estrone formation from estradiol-17 beta was demonstrated in all tissues. The formation of estradiol-17 beta from estrone was demonstrated in most tissues, however, it was barely detected or was undetectable in the glandular stomach, small intestine, cecum, and large intestine. Thus, 17 beta-hydroxysteroid oxidoreductase activity is expressed in all BALB/c mouse organs and tissues. Approximately two-thirds of the tissues and organs examined, including those of the reproductive tracts, favored the conversion of estrone to estradiol-17 beta rather than the reverse reaction. The results of this study, however, represent qualitative estimates of 17 beta-hydroxysteroid oxidoreductase activity in BALB/c mouse tissues that are uncorrected for conversion to hydroxylated metabolites. These in vitro findings suggest that the 17 beta-hydroxysteroid oxidoreductase catalyzed reduction of estrone may contribute to the maintenance of physiologic levels of estradiol-17 beta in estrogen responsive tissues.

[Studies on the diagnostic value of various enzymatic activties in icterogenic hepatitis of infancy. II. Sorbitol dehydrogenase, guanase and argininosuccinate lyase]. / Ricerche sul valore diagnostico di alcune attività enzimatiche nell'epatite itterigena dell'infanzia. II. Sorbitolodeidrogenasi, guanasi, argininsuccinatoliasi

The AA. have determined the levels of argininesuccinatolyase (ASAL), sorbitoldehydrogenase (SDH) and guanase (GUA) in 65 cases of hepatitis of infancy, by comparison with the corresponding levels of transaminases. Of all the enzymes examined, transaminases were the most sensitive sign of liver damage, not only because of their more pronounced rise in the earlier stages of the disease, but also in consideration of their slower regression to normal values. The AA. nevertheless believe that a special significance can be assigned to the determination of SDH for its persistency to levels higher than the normal ones in prolonged hepatitis, and for its quick increase in the recurrences; its regression to normal values may be assumed as an early and clear sign for the demonstration of the stages indicative of recovery.