Estrogen regulates progesterone production by human placental trophoblast cells in culture
We have suggested that estrogen regulates placental low-density lipoprotein (LDL) uptake and thus progesterone (P{sub 4}) production during primate pregnancy based on results obtained in antiestrogen-treated baboons. The objectives of the present study, were to determine whether estrogen is also important to regulation of P{sub 4} formation by the human placenta, and whether effects of estrogen were mediated by availability of cholesterol substrate via the LDL, de novo, or deesterification pathways. Term human placenta were dispersed in 0.125% trypsin, cytotrophoblasts were purified via a 70-5% Percoll gradient, incubated 72 h in DMEM with 10% FBS to stimulate formation of syncytia, then incubated an additional 48 h with estradiol (E2). In Experiment 1, 1 {mu}g/ml E{sub 2} and 500 {mu}g/MI LDL-protein, stimulated P{sub 4} (P < .05) two-fold above that with LDL alone, suggesting that E{sub 2} increased LDL uptake. Scatchard analysis indicated that trophoblast uptake of ({sup 125}I)LDL (ng/mg cell protein) was 50% greater (P < .05) with E{sub 2} (mean {plus minus} SE, 638 +/- 23; n = 6) than DMEM in the presence of antiestrogen MER-25. Moreover, uptake and degradation of LDL, and cellular content of free and esterified cholesterol, increased in a dose-dependent manner with 0.1 to 1000 ng/ml E{sub 2}. These results suggest that estrogen regulates placental cell uptake of LDL and thus availability of cholesterol for P{sub 4} biosynthesis during human pregnancy. In Experiment 2, E{sub 2} Stimulated P{sub 4} formation (ng/mg cell protein/48 h) from a control level of 194 {plus minus} 25 to 357 {plus minus} 62, in the absence of LDL. Under these conditions, cholesterol for P{sub 4} biosynthesis must have been derived from de novo synthesis and/or deesterification of cholesteryl ester stores.
- Research Organization:
- Maryland Univ., Baltimore, MD (USA)
- OSTI ID:
- 6159225
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ESTROGENS
BIOCHEMICAL REACTION KINETICS
PROGESTERONE
BIOSYNTHESIS
BIOLOGICAL PATHWAYS
CELL CULTURES
CHOLESTEROL
DOSE-RESPONSE RELATIONSHIPS
ESTERIFICATION
LIPOPROTEINS
MAN
PLACENTA
PREGNANCY
TRACER TECHNIQUES
ANIMALS
CHEMICAL REACTIONS
FETAL MEMBRANES
HORMONES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
LIPIDS
MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
PREGNANES
PRIMATES
PROTEINS
REACTION KINETICS
STEROID HORMONES
STEROIDS
STEROLS
SYNTHESIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques