283 METABOLISM OF PROSTAGLANDIN ENDOPEROXIDE (PGHp) IN HUMAN NEONATAL TISSUES

Abstract

The endoperoxide PGH2 serves as a common intermediate for the enzymatic production of prostaglandins (PG) E2, F2α, thromboxane (Tx) A2, and prostacyclin (PGI2). These compounds have diverse physiological activities and regulate numerous functions in various tissues and organs. Therefore, the distribution of individual enzymes responsible for the bioconversion of PGH2 into these compounds was investigated. Biopsies from lung, kidney, brain, cardiovascular system (CVS), the gastrointestinal tract (GIT), liver, pancreas and adrenal were obtained within one hour of abortion of human fetuses at 14, 16 and 21 weeks of gestation (WG). (14C) PGH2 was incubated with a microsomal fraction from each tissue homogenate. The products were isolated and identified by thin layer chromatogprahy and scintillation counting. The formation of PGE2, PGF2α, TxA2 (measured as TxB2) and PGI2 (measured as 6-keto PGF1α) in lung and kidney was demonstrated in 16 WG fetus. In addition, the formation of these compounds in the CVS and GIT was detected by 21 WG. Azo analog I inhibited biosynthesis of these compounds in duplicate incubations. The dominating pathway for PGH2 transformation varied among tissues which frequently possesses more than one enzyme catalyzing PGH2. The observation of PGH2 metabolism early in gestation strongly suggests an important role for these hormones in the physiology and maturation of the human fetus.