Aged PROP1 Deficient Dwarf Mice Maintain ACTH Production

Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD) that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH) deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1null (Prop1-/-) and the Ames dwarf (Prop1df/df) mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism

Therapeutic targeting of SDHB- mutated pheochromocytoma/paraganglioma with pharmacologic ascorbic acid

International audienc

Population-based case-control study revealed metabolomic biomarkers of suboptimal health status in Chinese population—potential utility for innovative approach by predictive, preventive, and personalized medicine

Background: Suboptimal health status (SHS) is a subclinical stage of chronic diseases, and the identification of SHS provides an opportunity for the predictive, preventive, and personalized medicine (PPPM) of chronic diseases. Previous studies have reported the associations between metabolic signatures and early signs of chronic diseases. Methods: This study aimed to detect the metabolic biomarkers for the identification of SHS in a case-control study. SHS questionnaire-25 (SHSQ-25) was used in a population-based health survey to measure the SHS levels of participants. The liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was conducted on plasma samples collected from 50 SHS participants and 50 age- and sex-matched healthy controls. Results: After adjusting for the confounders, 24 significantly differential metabolites, such as sphingomyelin, sphingosine, sphinganine, progesterone, pregnanolone, and bilirubin, were identified as the candidate biomarkers for SHS. Pathway analysis revealed that sphingolipid metabolism, taurine metabolism, and steroid hormone biosynthesis are the disturbed metabolic pathways related to SHS. A combination of four metabolic biomarkers (sphingosine, pregnanolone, taurolithocholate sulfate, cervonyl carnitine) can distinguish SHS individuals from the controls with a sensitivity of 94.0%, a specificity of 90.0%, and an area under the receiver operating characteristic curve of 0.977. Conclusion: Plasma metabolites are valuable biomarkers for SHS identification, and meanwhile, SHSQ-25 can be used as an alternative health screening tool in the population-based health survey. SHS-related metabolic disturbances could be detected at the early onset of SHS, and SHS-related metabolites could create a window opportunity for PPPM of chronic diseases