Ethanol decreases progesterone synthesis in human placental cells: mechanism of ethanol effect.
Fetal alcohol syndrome (FAS) is a set of signs and symptoms in offsprings born to mothers who abuse alcohol during pregnancy. We postulated that impairment in the placental endocrine function contribute to FAS. In this study, we examined in vitro effects of ethanol on the placental cells' (cytotrophoblast cells) capacity to synthesize progesterone. Cytotrophoblast cells were isolated from normal term placenta and were incubated (2 x 10(6)) with 20-, 30-, and 40-mM doses of ethanol for 6 h. Progesterone was measured in the incubate by RIA. The results showed that, at the 20-mM dose of ethanol, progesterone synthesis was significantly decreased (p less than 0.01), at the 30-mM dose level there was a further decrease of 20%. The differences between 30- and 40-mM ethanol dose levels were not significant. To determine the mechanism of ethanol effects on progesterone synthesis, cytotrophoblast cells were preincubated with 30 mM ethanol followed by 10 microliters of LDL (10 microliters LDL = 80 micrograms cholesterol) and vice versa. The results showed that ethanol effects on progesterone synthesis was dependent on whether ethanol was added prior to or following the addition of LDL in the medium. If ethanol was added in the medium prior to LDL, progesterone synthesis was decreased significantly (p greater than 0.01); however, when ethanol was added after the LDL, ethanol had no effect on progesterone synthesis. In the experiment where ethanol and LDL were added simultaneously in the medium, ethanol blunted the stimulatory effect of LDL on progesterone synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Ahluwalia
B
B
Department of Obstetrics and Gynecology, Howard University College of Medicine, Washington, DC 20059.
Smith
D
D
Adeyiga
O
O
Akbasak
B
B
Rajguru
S
S
D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis*; D011973:Receptors, LDL / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D000431:Ethanol; D011374:Progesterone