ABSTRACT
Luteal metabolism was investigated in corpora lutea of early pregnant rats treated with four abortifacient agents. In corpora lutea of rats treated with prostaglandin F2alpha or of rats 1 day postpartum, glucose-6-phosphate dehydrogenase (G6PDH) activity increased 140 to 170% and 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) was activated to significantly high levels, whereas malic enzyme activity decreased to 29% of control values. In aminoglutethimide-treated rats, the activities of G6PDH and malic enzyme decreased, while 20alpha-HSD activity was maintained at a very low level. With the increased dose, complete abortion was observed. In corpora lutea of these aborted rats, 20alpha-HSD was activated moderately and G6PDH values were slightly higher than control values, whereas malic enzyme activity fell to lower levels. All rats treated with clomiphene citrate aborted within 63 hours after the last injection. The activities of G6PDH, malic enzyme, and ATP citrate lyase in these corpora lutea decreased to 66, 68, and 72% of control levels, respectively; 20alpha-HSD activity was maintained at a very low level, and activities of 3beta-hydroxysteroid dehydrogenase, 6-phosphogluconate dehydrogenase, and pyruvate kinase were not appreciably altered. These findings indicated that, at the beginning of luteolysis and fetal resorption, the activities of steroidogenic enzymes decreased and 20alpha-HSD was not yet activated. Therefore, we could gauge the early changes of luteolysis by measuring the activities of G6PDH, MALIC ENZYME, AND ATP citrate lyase as well as 20alpha-HSD.
PIP: An enzymologic study of corpora lutea in early pregnant rats treated with abortifacient agents is presented. Prostaglandin F2 alpha treatmen t (500 mcg twice daily 3 or 4 consecutive times) revealed an increase in corpora lutea glucose-6-phosphate dehydrogenase (G6PDH) activity of 110-140% and a moderate increase in 20 alpha-hydroxysteroid dehydrogenas e (20 alpha-HSD), whereas malic enzyme decreased to 27% of control values. Aminoglutethimide treatment (10-20 mg twice daily 6 or 7 consecutive times) revealed decreased G6PDH and malic enzyme activities while 20 alpha-HSD activity was maintained at a very low level. Corpora lutea of these aborted rats revealed moderately active 20 alpha-HSD valu es and slightly higher than control values for G6PDH, whereas malic enzy me activity fell to lower levels. Clomiphene citrate treatment (.5 ml of 3 mg/ml or .5 ml plus .5 ml of 10 mg/ml progesterone) caused abortion within 63 hours postinjection. G6PDH, malic enzyme, and adenosine triphosphate (ATP) citrate lyase activities in these corpora lutea decreased to 66, 68, and 72% of control levels, respectively, while 20 alpha-HSD activity was maintained at a very low level. Activities of 3beta hydroxysteroid dehydrogenase, 6-phosphogluconate dehydrogenase and pyruvate kinase were not appreciably altered. These results indicate that at the beginning of luteolysis and fetal resorption the activities of steroidogenic enzymes decreased and 20 alpha-HSD was not yet activated. Therefore, G6PDH, malic enzyme, and ATP citrate lyase activities could be measured to gauge early changes of luteolysis.
Subject(s)
Abortifacient Agents/pharmacology , Corpus Luteum/enzymology , ATP Citrate (pro-S)-Lyase/metabolism , Aminoglutethimide/pharmacology , Animals , Clomiphene/pharmacology , Corpus Luteum/drug effects , Estradiol/pharmacology , Female , Glucosephosphate Dehydrogenase/metabolism , Hydroxysteroid Dehydrogenases/metabolism , Malate Dehydrogenase/metabolism , Oxidoreductases/metabolism , Phosphogluconate Dehydrogenase/metabolism , Pregnancy , Prostaglandins F/pharmacology , RatsABSTRACT
Human corpora lutea of pregnancy obtained at 5 to 11 weeks of gestation were incubated in vitro in the presence of various concentrations of human chorionic gonadotropin (hCG) and prostaglandin F2alpha (PGF2alpha). Progesterone (P) and 17beta-estradiol (E2) released into the medium during incubation were measured by radioimmunoassay. Pieces of the corpora lutea were also examined ultrastructurally before and after incubation. Release of P and E2 into the medium was significantly increased by the addition of hCG and PGF2alpha in some cases. However, the response to hCG and PGF2alpha appeared to vary according to the age of the corpus luteum. Ultrastructurally, the lutein cells were well maintained with respect to the appearance of the smooth endoplasmic reticulum and mitochondria after 120-min incubations. On the basis of these observations, the following conclusions have been reached: 1) This incubation system seems to be suitable for investigating the direct effects of chemicals on lutein cells in vitro. 2) Both hCG and PFG2alpha directly stimulate steroidogenesis in the human corpus luteum of pregnancy, demonstrating their luteotropic actions in vitro. 3) Observed variations in P and E2 secretion might have been due to the different activities of aromatizing enzymes at different stages of gestation.
