Effects of prenatal Leydig cell function on the ratio of the second to fourth digit lengths in school-aged children.

Prenatal sex hormones can induce abnormalities in the reproductive system and adversely impact on genital development. We investigated whether sex hormones in cord blood influenced the ratio of the second to fourth digit lengths (2D/4D) in school-aged children. Of the 514 children who participated in a prospective cohort study on birth in Sapporo between 2002 and 2005, the following sex hormone levels were measured in 294 stored cord blood samples (135 boys and 159 girls); testosterone (T), estradiol (E), progesterone, LH, FSH, inhibin B, and insulin-like factor 3 (INSL3). A total of 350 children, who were of school age and could be contacted for this survey, were then requested via mail to send black-and-white photocopies of the palms of both the left and right hands. 2D/4D was calculated in 190 children (88 boys and 102 girls) using photocopies and derived from participants with the characteristics of older mothers, a higher annual household income, higher educational level, and fewer smokers among family members. 2D/4D was significantly lower in males than in females (p<0.01). In the 294 stored cord blood samples, T, T/E, LH, FSH, Inhibin B, and INSL3 levels were significantly higher in samples collected from males than those from females. A multivariate regression model revealed that 2D/4D negatively correlated with INSL3 in males and was significantly higher in males with <0.32 ng/mL of INSL3 (p<0.01). No correlations were observed between other hormones and 2D/4D. In conclusion, 2D/4D in school-aged children, which was significantly lower in males than in females, was affected by prenatal Leydig cell function

The 17,18-epoxyeicosatetraenoic acid–G protein–coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques

Background: Metabolites of eicosapentaenoic acid exert various physiologic actions. 17, 18-Epoxyeicosatetraenoic acid (17, 18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated.Objective: We evaluated the effectiveness of 17, 18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17, 18-EpETE.Methods: Contact hypersensitivity was induced by topical application of 2, 4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17, 18-EpETE was identified by using the TGF-α shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17, 18-EpETE was examined by using KO mice and specific inhibitor treatment.Results: We found that preventive or therapeutic treatment with 17, 18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17, 18-EpETE was recognized by G protein–coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17, 18-EpETE was abolished in the absence or inhibition of GPR40.Conclusion: 17, 18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases

Relationship between 2D/4D and sex hormones in cord blood.

<p>Relationship between 2D/4D and sex hormones in cord blood.</p

Patient characteristics.

<p>Patient characteristics.</p

2D/4D and INSL3.

<p>2D/4D was significantly higher in males with <0.32 ng/mL of INSL3 in cord blood (p<0.01). **: p<0.01.</p

Sex hormone levels in cord blood in males and females.

<p>Sex hormone levels in cord blood in males and females.</p

Sex hormones in cord blood and 2D/4D.

<p>Sex hormones in cord blood and 2D/4D.</p

2D/4D in right hands, left hands, and mean values.

<p>2D/4D in right hands, left hands, and mean values were significantly higher in females than in males.</p