BackgroundInsufficient vitamin D activity has attracted increasing interest as a possible underlying risk factor in disorders of the central nervous system, including autism.MethodsIn this study, 25-hydroxyvitamin D (25(OH)D) was analysed in 58 Sweden-born sibling pairs, in which one child had autism spectrum disorder (ASD) and the other did not. The study group consisted of two representative samples; 47 Gothenburg sibling pairs with mixed ethnicities and 11 Stockholm sibling pairs with Somali background. 25(OH)D levels were analysed in the stored dried blood spots taken in the neonatal period for metabolic screening.ResultsThe collapsed group of children with ASD had significantly lower vitamin D levels (M = 24.0 nM, SD = 19.6) as compared with their siblings (M = 31.9 nM, SD = 27.7), according to a paired samples t-test (P = 0.013). The difference was - most likely - not only accounted for by a difference in season of birth between ASD and non-ASD siblings since the mean 25(OH)D levels differed with similar effect size between the sibling pairs born during winter and summer, respectively. All children with African/Middle East background, both the children with ASD and their non-ASD siblings, had vitamin D deficiency.ConclusionsThe findings suggest that low prenatal vitamin D may act as a risk factor for ASD, however, there is a need for replication with larger samples. Future research should study whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring.

Previously, we reported that androgen receptor (AR), but not estrogen receptor (ER) or progesterone receptor (PR), is predictive of response to the synthetic progestin, medroxyprogesterone acetate (MPA), in a cohort of 83 patients with metastatic breast cancer. To further investigate the role of AR in determining response to MPA in this cohort, we analyzed AR levels by immunohistochemistry with two discrete antisera directed at either the NH 2 or the COOH termini of the receptor. Compared with tumors that responded to MPA (n = 31), there was a significant decrease in the intensity and extent of AR immunoreactivity with both AR antisera in tumors from nonresponders (n = 52). Whereas only a single AR immunostaining pattern was detected in responders to MPA, reflecting concordance of immunoreactivity with the two AR antisera, tumors from nonresponders exhibited four distinct AR immunostaining patterns: (a) concordance with the two antibodies (31%), (b) staining only with the COOH-terminal antibody (33%), (c) staining only with the NH 2 -terminal antibody (22%), or (d) no immunoreactivity with either NH 2 -or COOH-terminal antibody (14%). DNA sequencing and functional analysis identified inactivating missense gene mutations in the ligand-binding domain of the AR in tumors from two of nine nonresponders positive with the NH 2 -terminal AR antisera but negative for COOH-terminal immunoreactivity and lacking specific, high-affinity dihydrotestosterone binding in tumor cytosol fractions. Tumors with more AR than the median level (37 fmol/mg protein) had significantly lower levels of PR (30 fmol/mg protein) than tumors with low AR (PR; 127 fmol/mg protein) despite comparable levels of ER. Ligand-dependent activation of the AR in human T47D and MCF-7 breast cancer cells resulted in inhibition of estradiol-stimulated cell proliferation and a reduction in the capacity of the ER to induce expression of the PR. These effects could be reversed using a specific AR antisense oligonucleotide. Increasing the ratio of AR to ER resulted in a greater androgen-dependent inhibition of ER function. Collectively, these data suggest that reduced levels of AR or impaired AR function contribute to the failure of MPA therapy potentially due to abrogation of the inhibitory effect of AR on ER signaling. (Cancer Res 2005; 65(18): 8487-96)

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