Thyroid diseases are more prevalent in women, particularly between puberty and menopause. It is wellknown that estrogen (E) has indirect effects on the thyroid economy. Direct effects of this steroid hormone on thyroid cells have been described more recently; so, the aim of the present paper was to review the evidences of these effects on thyroid function and growth regulation, and its mechanisms. The expression and ratios of the two E receptors,αandβ, that mediate the genomic effects of E on normal and abnormal thyroid tissue were also reviewed, as well as nongenomic, distinct molecular pathways. Several evidences support the hypothesis that E has a direct role in thyroid follicular cells; understanding its influence on the growth and function of the thyroid in normal and abnormal conditions can potentially provide new targets for the treatment of thyroid diseases.

Context: Vitamin D is frequently prescribed as a supplement, yet its absorption remains poorly understood. Objective: This systematic review was performed to evaluate data on mechanisms involved in the intestinal absorption of vitamin D. Data Sources: PubMed, Embase, and Cochrane Library databases were searched. Study Selection: The following studies were included: experimental laboratory studies of vitamin D absorption through the enterocyte brush-border membrane; absorption tests that used radiolabeled vitamin D; and clinical trials in adults that investigated a single dose of cholecalciferol or ergocalciferol and reported at least 2 measurements of serum cholecalciferol, ergocalciferol, or 25-hydroxyvitamin D. Data Extraction: From 2069 articles identified, 46 met the inclusion criteria. Results: Different methods were employed to evaluate vitamin D absorption. Recent research suggests that vitamin D absorption is not an exclusive simple diffusion process. Vitamin D was better absorbed when it was consumed with fat-containing meals, but absorption also occurred without fat or oily vehicles. Factors that modified cholesterol absorption also altered vitamin D absorption. Conclusion: Vitamin D is probably absorbed through passive diffusion and a mechanism involving membrane carriers, especially cholesterol transporters, although data remain scarce. Some data suggest that fat, when consumed concomitantly with vitamin D, improves vitamin D absorption.

Case Report from JAMA Internal Medicine — Hypomagnesemia and Proton Pump Inhibitors — Below the Tip of the Iceberg

Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies associated with significant morbidity and mortality. Although multiple studies have contributed to a better understanding of the genetic alterations underlying this frequently arising disease, the downstream molecular effectors that impact PTC pathogenesis remain to be further defined. Here, we report that the regulator of cell fate specification, PROX1, becomes inactivated in PTC through mRNA downregulation and cytoplasmic mislocalization. Expression studies in clinical specimens revealed that aberrantly activated NOTCH signaling promoted PROX1 downregulation and that cytoplasmic mislocalization significantly altered PROX1 protein stability. Importantly, restoration of PROX1 activity in thyroid carcinoma cells revealed that PROX1 not only enhanced Wnt/β-catenin signaling but also regulated several genes known to be associated with PTC, including thyroid cancer protein (TC)-1, SERPINA1, and FABP4. Furthermore, PROX1 reexpression suppressed the malignant phenotypes of thyroid carcinoma cells, such as proliferation, motility, adhesion, invasion, anchorage-independent growth, and polyploidy. Moreover, animal xenograft studies demonstrated that restoration of PROX1 severely impeded tumor formation and suppressed the invasiveness and the nuclear/cytoplasmic ratio of PTC cells. Taken together, our findings demonstrate that NOTCH-induced PROX1 inactivation significantly promotes the malignant behavior of thyroid carcinoma and suggest that PROX1 reactivation may represent a potential therapeutic strategy to attenuate disease progression Cancer Res; 76(3); 582–93. ©2015 AACR.