Genetic evidence of the programming of beta cell mass and function by glucocorticoids in mice.

AIMS/HYPOTHESIS: Prenatal exposure to excess glucocorticoids associates with low birthweight in rodents, primates and humans and its involvement in programming glucose homeostasis is suspected. Our aim was to further dissect the role of glucocorticoids on beta cell development and function in mice. METHODS: Using the model of maternal general food restriction during the last week of pregnancy, we thoroughly studied in the CD1 mouse-mothers and fetal and adult offspring--the pancreatic, metabolic and molecular consequences of maternal undernutrition associated with excess glucocorticoids. The specific involvement of the glucocorticoid receptor (GR) was studied in mutant fetuses lacking GR in pancreatic precursors or mature beta cells. RESULTS: Maternal general food restriction in the mouse is associated with decreased maternal glucose and increased corticosterone levels. Fetuses from underfed dams had increased corticosterone levels, decreased pancreatic endocrine gene expression but increased exocrine gene expression and a lower beta cell mass. The offspring of these dams had a low birthweight, permanent postnatal growth retardation and, as adults, impaired glucose tolerance, decreased beta cell mass (-50%) and massively reduced islet expression (-80%) of most of the genes involved in beta cell function (e.g. Pdx1, Sur1 [also known as Abcc8], insulin). Moreover, using mutant fetuses lacking GR in pancreatic precursors or beta cells we show that the deleterious effect of undernutrition on fetal beta cell development requires the presence of the GR in pancreatic precursor cells. CONCLUSIONS/INTERPRETATION: These results demonstrate the crucial role of excess fetal glucocorticoids and the importance of GR signalling in progenitor cells to programme beta cell mass and dysfunction.

Mosaic 46,XY/92,XXYY,del(5)(q13 q34) in an adult lymphoblastic leukemia.

Usually the chromosome anomalies encountered in ALL are modal number abnormalities (hyperdiploidy or hypodiploidy) and structural anomalies such as t(8;14), t(11;14), t(9;22), t(1;19) and del(6p). The 5q- syndrome is mainly associated with myelodysplastic syndromes and with ANLL (M1, M2, M3). We report the case of a patient presenting with a mosaic karyotype 46,XY/92,XXYY,del(5)(q13 q34) in the following proportion 1/3 normal mitoses and 2/3 tetraploid mitoses.

Secretory proteins of human seminal vesicles and their relationship to lipids and sugars.

Proteins secreted by human seminal vesicles are strongly positively charged. Cellulose acetate electrophoresis show how the presence of two protein bands of vesicular origin (N3 and N4). When studied on SDS-PAGE there are three main bands of molecular weight 67, 45 and 40 kDa, respectively. These proteins may be separated by a chromatographic process using gel filtration on Sephadex G 25 M and ion exchange chromatography on CM and SP Sephadex C 50. Fructose, secreted by seminal vesicles, is excreted with specific proteins and these complexes take part to coagulum formation. During liquefaction glucose appears progressively and fructose is released from complexes with proteins. Interconversion processes that transform fructose into glucose, originate from prostatic secretion. In man, the liquefaction process seems to be not due to proteolysis, but by the way of other mechanisms that transform vesicular proteins of very high molecular weight into sub-units with lower molecular weights in the first minutes after ejaculation. In species other than man, i.e. lemurian, fructose takes part in the coagulation process with other components (albumin, ions, -SH groups). Cholesterol appears to be in relation with proteins which have high molecular weights. Half of phospholipid content of seminal plasma is probably free. Incubation of seminal plasma with spermatozoa show that these cells use triglycerides for their metabolism. The ratio between cholesterol and phospholipids is an important marker for the capacitation-decapacitation process.