Hyperprostaglandin E syndrome (HPS), the prenatal variant of
Bartter's syndrome, is characterized by a marked and selective stimulation of
prostaglandin E (
PGE2) synthesis. In the study group HPS patients showed increased urinary levels of
PGE2, an index of renal, and of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic
acid (
PGE-M), an index of systemic
PGE2 synthesis of 470% and of 570%, respectively. In addition, plasma concentration of
PGE-M was also elevated 6.3-fold when compared with a control group. The urinary levels of other
prostanoids were unaltered. During
indomethacin treatment in both groups
prostanoid excretion rates were suppressed to similar levels. To investigate the origin of stimulated
prostanoid biosynthesis in HPS patients CD14+ monocytes were isolated from plasma samples, and the
prostanoid synthesis was analyzed. The pattern and amounts of metabolites synthesized from endogenous
arachidonic acid pools did not vary significantly between monocytes of the HPS and the control group.
Thromboxane A2 (TXA2) was formed as the major
prostanoid product. Using
PGH2 as an exogenous substrate, again no difference in
PGE2 biosynthesis was observed, indicating no difference in
PGE-synthetic activity between both groups. Additionally,
mRNA expression analysis of CD14+ monocytes via RT-PCR delineated the constitutive expression of
cyclooxygenase-1,
cyclooxygenase-2, and
thromboxane synthase
mRNA in cells from HPS patients and controls without statistical differences between these two groups. In conclusion, our data show that monocytes are not the source for the increased
PGE2 biosynthesis in children with HPS, and a genetic defect in
PGE synthesis can be excluded as the primary event in the pathogenesis in HPS.