This paper reports the clinical and genetic characteristics of a case of combined pituitary hormone deficiency type I (CPHD1) caused by POU domain, class 1, transcription factor 1 (POU1F1) gene variation. A 2 years and 3 months old girl mainly presented with short stature, special facial features of prominent forehead, enophthalmos, and short mandible, loose skin, central hypothyroidism, complete growth hormone deficiency, and anterior pituitary hypoplasia. Gene analysis identified a novel heterozygous mutation, c.889C>T (p.R297W), in POU1F1 gene, and this locus of her parents was wild-type. This mutation was analyzed as a possible pathogenic variant according to the guidelines of the American College of Medical Genetics and Genomics, which has not been previously reported in the literature and conforms to the autosomal dominant inheritance. This child was diagnosed with CPHD1. Her height increased by 19.8 cm and showed a catch-up growth trend after one year of combined treatment with growth hormone and euthyrox. This study enriches the mutation spectrum of POU1F1 gene and has important significance for the diagnosis and classification of combined pituitary hormone deficiency.
Child, Preschool ; Female ; Humans ; Hypopituitarism ; Mutation ; Transcription Factor Pit-1 ; Transcription Factors

OBJECTIVEThis study aimed to investigate the susceptibility of mice with streptozotocin(STZ)-induced diabetes mellitus (TIDM) to the uptake of pentavalent inorganic arsenic (iAsV) and the possible molecular mechanism.

METHODSTIDM was induced in mice by STZ. TIDM and normal mice were treated with 15.0 mg/kg Na2HAsO4·12H2O by intragastric administration. Then, the concentrations of arsenic in various tissues were measured by atomic fluorescence spectrometry. The gene expression levels of Pit1 and Pit2 were quantified by real-time RT-PCR, and their protein levels were detected by Western blotting in mouse heart, kidney, and liver tissues.

RESULTSThe concentrations of arsenic in STZ-induced TIDM mouse tissues were higher at 2 h after intragastric administration of Na2HAsO4·12H2O. Compared with the levels in normal mice, PIT1 and PIT2, which play a role in the uptake of iAsV, were upregulated in the livers and hearts of TIDM mice. PIT1 but not PIT2 was higher in TIDM mouse kidneys. The upregulation of Pit1 and Pit2 expression could be reversed by insulin treatment.

CONCLUSIONThe increased uptake of iAsV in TIDM mouse tissues may be associated with increased PIT1 and/or PIT2 expression.

Animals ; Arsenic ; pharmacokinetics ; Diabetes Mellitus, Experimental ; metabolism ; Environmental Pollutants ; pharmacokinetics ; Gene Expression Regulation ; physiology ; Male ; Mice ; Mice, Inbred ICR ; Sodium-Phosphate Cotransporter Proteins, Type III ; genetics ; metabolism ; Transcription Factor Pit-1 ; genetics ; metabolism

OBJECTIVETo elucidate the effect of interleukin-1 beta (IL-1 beta) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S.

METHODSStably transfected MtT/S cells were firstly established by transfecting 484-Luc1 plasmid which contained hGH gene promoter -484 to +30 bp and luciferase reporter gene. The effect of IL-1 beta on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells.

RESULTSThe 10(3) U/mL IL-1 beta stimulated secretion and synthesis of GH, and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 micromol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL-1 beta, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly abolished the effect of IL-1 beta. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected induction of hGH promoter activity by IL-1 beta. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1 beta, and results showed that the stimulatory effect of IL-1 beta was abolished following deletion of the -196 to -132 bp fragment.

CONCLUSIONSIL-1 beta promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1 beta on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.

Animals ; Cell Line ; Enzyme Inhibitors ; metabolism ; Human Growth Hormone ; genetics ; metabolism ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Promoter Regions, Genetic ; Rats ; Receptors, Interleukin-1 ; genetics ; metabolism ; Somatotrophs ; cytology ; physiology ; Transcription Factor Pit-1 ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism