Fetoplacental unit involvement in uric acid production in women with severe preeclampsia: a prospective case control pilot study.

Purpose: Preeclampsia (PE) is a common complication of pregnancy that carries significant risks for both the mother and the fetus, and is frequently accompanied by hyperuricemia, yet the exact source of elevated uric acid (UA) levels remains partially elucidated. Several potential origins for increased UA levels include abnormal renal function, increased tissue breakdown, and increased activity of the enzyme Xanthine Oxidase (XO). The aim of the study was to determine serum levels of UA and XO not only in maternal serum, but also in umbilical vein (UV) and umbilical artery (UA) and explore their possible role in PE development.

Gi and RGS proteins provide biochemical control of androgen receptor nuclear exclusion.

Nuclear localization of androgen receptors (ARs) is essential for their activity. Melatonin induces AR nuclear exclusion via increase in cGMP, calcium, and protein kinase C (PKC) activation, presumably through G-protein(s). The effects of regulators of G-protein signaling (RGS) on AR localization were studied in AR-expressing PC3 cells.

Differential effects of melatonin and its downstream effector PKCalpha on subcellular localization of RGS proteins.

Regulators of G protein signaling (RGS) are proteins that bind specifically to activated Galpha subunits of heterotrimeric G proteins to terminate signaling by both Galpha and Gbetagamma subunits. Signal-induced RGS redistribution may affect their activity in G protein-mediated signaling. We have previously shown that melatonin and the cell permeable cGMP analog 8-bromo cGMP, which lead to protein kinase C (PKC) activation, enhanced cytoplasmic distribution of RGS10 and RGS2 in prostate carcinoma PC3-AR cells.

Nuclear exclusion of the androgen receptor by melatonin.

Androgen receptors (AR) play a crucial role in androgen-mediated processes and prostate cancer progression. The pineal hormone melatonin attenuates the androgen-dependent growth of benign and cancer prostate epithelial cells in vitro and may reverse clinical resistance to androgen ablation therapy in patients progressing on gonadotropin releasing hormone (GnRH) analogue. Where along the AR cascade does melatonin act remains to be determined.

Differential regulation by melatonin of cell growth and androgen receptor binding to the androgen response element in prostate cancer cells.

Objectives: The pineal hormone melatonin inhibits the growth of benign human prostate epithelial cells and the androgen-dependent prostate cancer LNCaP cells. In the androgen-nonresponsive prostate carcinoma PC3 cells melatonin inhibits cell growth only at high but not low cell density. We have recently found that melatonin causes nuclear exclusion of the AR and attenuates it transcriptional activity in LNCaP cells as well as PC3 cells stably transfected with a wild type AR expressing vector (PC3-AR).