Unexpected severe consequences of Pikfyve deletion by aP2- or Aq-promoter-driven Cre expression for glucose homeostasis and mammary gland development.

Systemic deficiency of PIKfyve, the evolutionarily conserved phosphoinositide kinase synthesizing cellular PtdIns5P and PtdIns(3,5)P2 and implicated in insulin signaling, causes early embryonic death in mice. In contrast, mice with muscle-specific Pikfyve disruption have normal lifespan but exhibit early-age whole-body glucose intolerance and muscle insulin resistance, thus establishing the key role of muscle PIKfyve in glucose homeostasis. Fat and muscle tissues control postprandial glucose clearance through different mechanisms, raising questions as to whether adipose Pikfyve disruption will also trigger whole-body metabolic abnormalities, and if so, what the mechanism might be.

Effect of prolactin on inositol uptake in mouse mammary gland explants.

Studies were carried out to assess the role of insulin (I), cortisol (H), and prolactin (P or PRL) in regulating myoinositol (inositol) uptake in the mammary gland. Using cultured mammary gland explants from pregnant mice (12-14 days into gestation), insulin and prolactin were found to stimulate inositol uptake, while cortisol impaired inositol uptake. Optimal inositol uptake was observed when tissues were treated with all three lactogenic hormones (I, H, and PRL).

Hormone regulation of choline uptake and incorporation in mouse mammary gland explants.

Choline is a nutrient in milk that is essential for the nourishment and growth of newborns. In rat milk, choline is present in concentrations that are more than an order of magnitude higher than in maternal serum. Using cultured mammary tissues taken from 12-14-day pregnant mice, the effects of the three primary lactogenic hormones--prolactin (PRL), insulin (I), and cortisol (H)--on choline uptake and incorporation into lipids were determined.

Pendrin transporter carries out iodide uptake into MCF-7 human mammary cancer cells.

Previous studies have shown that iodide is actively taken up into mammary alveolar epithelial cells and secreted into milk. In the present studies we demonstrate that 125I also accumulates in MCF-7 cells against a concentration gradient; distribution ratios of greater than 30 were achieved. Iodide uptake into MCF-7 cells is transient, with peak accumulations occurring in about 5 min.

Prolactin, cortisol, and insulin regulation of nucleoside uptake into mouse mammary gland explants.

Nucleosides are essential components of milk that are used for the nourishment of newborns. Effects of the three primary lactogenic hormones, including prolactin (PRL), insulin (I), and cortisol (H), on nucleoside uptake and incorporation into cultured mammary tissues taken from 12- to 14-day pregnant mice were determined; most experiments focused on the regulation of uridine uptake. Insulin alone, as well as PRL in the presence of insulin and cortisol, was shown to stimulate uridine uptake and incorporation into RNA in mammary explants taken from 12- to 14-day pregnant mice.

Prolactin regulation of the pendrin-iodide transporter in the mammary gland.

Iodide is an essential constituent of milk that is present in concentrations more than an order of magnitude higher than in the maternal plasma. Earlier, a sodium-iodide symporter was identified in the mammary gland; this transporter is presumed to take iodide from the maternal plasma into the alveolar epithelial cells of the mammary gland. We now report the existence of a second iodide transporter, pendrin, which is also essential for iodide accumulation in milk.

Effect of prolactin on phosphate transport and incorporation in mouse mammary gland explants.

Inorganic phosphate is present in milk at a concentration that is severalfold higher than in maternal plasma. In cultured mammary tissues from 12- to 14-day-pregnant mice, the intracellular concentration of (32)PO(4) was six times higher than in the culture medium after a 4-h treatment with (32)PO(4). Of the principal lactogenic hormones [insulin (I), cortisol (H), and prolactin (PRL)], only I and PRL (in the presence of H and I) stimulated (32)PO(4) uptake into cultured mammary tissues; H, by itself or in the presence of I or PRL, inhibited (32)PO(4) uptake.

Effect of insulin on iodide uptake in mouse mammary gland explants.

Studies were carried out primarily to assess the role of insulin in regulating iodide uptake in the mammary gland. Using cultured mammary gland explants from virgin and pregnant mice (12-14 days into gestation), insulin (1 microg/ml) was shown to stimulate iodide uptake after a 2-day exposure period. The effect of insulin was manifested by itself, as well as in the presence of cortisol and prolactin.