Reference intervals for follicle-stimulating hormone, luteinizing hormone and prolactin in children and young adults on the bioMérieux Mini-Vidas system.

We measured serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin concentrations on a bioMérieux Mini Vidas system in a pediatric population ranging in age from 1 to 19 years. Reference intervals were established separately for females and males, with stratification by age group and by Tanner's pubertal stage. FSH values were higher in females than in males, and were lowest in both sexes of age class 2 (4-8 years), increasing thereafter to the upper limit for stage PIV (females) and stage PV (males). LH values showed a similar pattern of change: concentrations were lowest for class 1 (1-3 years) and class 2 (4-8 years), and highest for stage PII (females) and stage PV (males). No significant difference was observed according to gender. Prolactin values did not differ markedly according to gender or pubertal status.

Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene.

Methylmalonyl-CoA mutase (MCM) apoenzyme deficiency is a rare metabolic disease that may result in distinct biochemical phenotypes of methylmalonic acidemia (MMA), namely mut(o) and mut-. We analyzed a cohort of 40 MCM-deficient patients with MMA affected by either the mut(o) or the mut- form of the disease. By direct sequencing of cDNA and gDNA of the MUT gene, we detected 42 mutations, 29 of which were novel mutations. These included five frameshift mutations (insertion, deletion, or duplication of a single nucleotide), five sequence modifications in consensus splice sites, six nonsense and 12 missense mutations, and a large genomic deletion including exon 12. We explored how the 12 novel missense mutations might cause the observed phenotype by mapping them onto a three-dimensional model of the human MCM generated by homology with the P. shermanii enzyme. In this work we update the spectrum of MCM mutations (n=84), and then discuss their prevalence and distribution throughout the coding sequence in relation to the enzyme structure.

STAT5B-mediated growth hormone signaling is organized by highly dynamic microtubules in hepatic cells.

In the last decade, the notion that microtubules are critical to the spatial organization of signal transduction and contribute to the transmission of signals to downstream targets has been proposed. Because the STAT5B transduction and transcription factor is the major STAT protein activated by growth hormone stimulation in hepatocytes and is a crossroads between many signaling pathways, we studied the involvement of microtubules in STAT5B-mediated growth hormone signaling pathway in the highly differentiated and polarized WIF-B hepatic cell line. We showed that depolymerization of the microtubule network impaired STAT5B translocation to the nucleus upon growth hormone treatment. A significant amount of STAT5B binds to microtubules, while STAT5A and STAT3 are exclusively compartmentalized in the cytosol. Moreover, taxol-induced stabilization of microtubules released STAT5B from its binding, and we show that STAT5B binds specifically to the highly dynamic microtubules and is absent of the stable microtubule subpopulation. The specific involvement of dynamic microtubule subpopulation in growth hormone signaling pathway was confirmed by the inhibition of growth hormone-induced STAT5B nuclear translocation after stabilization of microtubules or specific disruption of highly dynamic microtubules. Upon growth hormone treatment, MT-bound STAT5B was rapidly released from microtubules by a dynein-dependent transport to the nucleus. Altogether, our findings indicate that the labile microtubule subpopulation specifically and dynamically organizes STAT5B-mediated growth hormone signaling in hepatic cells.