Pregnenolone production in pregnancy

Little, Brian; Billiar, Reinhart B.; Halla, Märta; Heinsons, A.; Jassani, Majida N.; Kline, Irene T.; Purdy, R. H.

doi:10.1016/0002-9378(71)90466-2

Cited by 13 publications

(5 citation statements)

References 17 publications

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“…Although a decline in 3␤-HSD mRNA transcripts was also observed following coculture with Cd, 3␤-HSD activity, which is abundant in human trophoblasts [39], was not significantly affected. Therefore, perhaps because of the high concentration of 3␤-HSD within human trophoblasts, coculture with the CdCl 2 concentrations tested in the present study had no significant effects on activity.…”

Section: Discussionmentioning

confidence: 92%

Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-Chain Cleavage and 3β-Hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts

Kawai

Swan

Green

et al. 2002

Biology of Reproduction

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We previously suggested that cadmium (Cd), an environmental toxicant and constituent of tobacco smoke, inhibits progesterone secretion in cultured human placental trophoblasts by inhibiting low-density lipoprotein receptor mRNA expression. In the current study, we investigated whether Cd also disrupts progesterone synthesis via P450 cholesterol side-chain cleavage (P450(scc)) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD), enzymes that play important roles in placental steroidogenesis. Human cytotrophoblasts were purified by density gradient centrifugation and incubated in Dulbecco modified Eagle medium + 10% fetal bovine serum with 0, 5, 10, or 20 microM CdCl(2) for 96 h. Cells progressed to syncytiotrophoblastic maturity regardless of treatment. No differences (P > 0.05) in cell protein and lactate dehydrogenase activity were observed between untreated trophoblasts and those treated with CdCl(2). However, P450(scc) and 3beta-HSD mRNA transcript levels declined in a dose-dependent manner (P <0.05) in trophoblasts cocultured with 5, 10, or 20 microM CdCl(2). P450(scc) activity was similarly inhibited (P < 0.05) by CdCl(2) treatment, although 3beta-HSD activity was not significantly affected. Coculture with 8-bromo-cAMP enhanced progesterone secretion in untreated cultures but did not reverse the decline in progesterone secretion induced by CdCl(2) treatment. CdCl(2) failed to influence cAMP content in cultured cells. Collectively, results suggest that P450(scc) enzyme is another site at which Cd interferes with placental progesterone production. However, it is unlikely that an inhibition of cAMP is involved with the inhibition of progesterone biosynthesis by Cd in human trophoblasts.

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Section: Discussionmentioning

confidence: 92%

Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-Chain Cleavage and 3β-Hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts

Kawai

Swan

Green

et al. 2002

Biology of Reproduction

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“…It has been proposed that accumulation of P450scc mRNA is mainly controlled by the cAMP-dependent pathway in human trophoblasts (72,75). Thus, the human P450scc gene promoter contains consensus sequences that match known positive cAMP-responsive elements (76,77).…”

Section: Estrogenic Effects Of CD 2 +mentioning

confidence: 99%

Endocrine Disruption by Cadmium, a Common Environmental Toxicant with Paradoxical Effects on Reproduction

Henson

Chedrese

2004

Exp Biol Med (Maywood)

438

231

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Cadmium (Cd(2+)) is a common environmental pollutant and a major constituent of tobacco smoke. Exposure to this heavy metal, which has no known beneficial physiological role, has been linked to a wide range of detrimental effects on mammalian reproduction. Intriguingly, depending on the identity of the steroidogenic tissue involved and the dosage used, it has been reported to either enhance or inhibit the biosynthesis of progesterone, a hormone that is inexorably linked to both normal ovarian cyclicity and the maintenance of pregnancy. Thus, Cd(2+) has been shown to exert significant effects on ovarian and reproductive tract morphology, with extremely low dosages reported to stimulate ovarian luteal progesterone biosynthesis and high dosages inhibiting it. In addition, Cd(2+) exposure during human pregnancy has been linked to decreased birth weights and premature birth, with the enhanced levels of placental Cd(2+) resulting from maternal exposure to industrial wastes or tobacco smoke being associated with decreased progesterone biosynthesis by the placental trophoblast. The stimulatory effects of Cd(2+) on ovarian progesterone synthesis, as revealed by the results of studies using stable porcine granulosa cells, appear centered on the enhanced conversion of cholesterol to pregnenolone by the cytochrome P450 side chain cleavage (P450scc). However, in the placenta, the Cd(2+)-induced decline in progesterone synthesis is commensurate with a decrease in P450scc. Additionally, placental low-density lipoprotein receptor (LDL-R) mRNA declines in response to Cd(2+) exposure, suggesting an inhibition in the pathway that provides cholesterol precursor from the maternal peripheral circulation. Potential mechanisms by which Cd(2+) may affect steroidogenesis include interference with the DNA binding zinc (Zn(2+))-finger motif through the substitution of Cd(2+) for Zn(2+) or by taking on the role of an endocrine disrupting chemical (EDC) that could mimic or inhibit the actions of endogenous estrogens. Divergent, tissue-specific (ovary vs. placenta) effects of Cd(2+) also cannot be ruled out. Therefore, in consideration of the data currently available and in light of the potentially serious consequences of environmental Cd(2+) exposure to human reproduction, we propose that priority should be given to studies dedicated to further elucidating the mechanisms involved.

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“…In vivo isotopic dilution studies indicate that A 5 P-S and A 5 P are in equilibrium analogous to estrone and estrone sulfate (22). As the production of A 5 P increased, an increase in the concentration of A 5 P-S might also be expected, as was observed.…”

Section: Corticoid Augmentable: a 5 P And A 5 P-smentioning

confidence: 56%

“…In vivo isotopic studies have suggested that A 5 P is primarily the product of placental conversion of maternal cholesterol (22). An increase in maternal A 5 P concentration is observed on initial treatment with cortisol, which persists but does not increase with retreatment and/or increased duration of treatment.…”

Section: Corticoid Augmentable: a 5 P And A 5 P-smentioning

confidence: 98%

Interrelationships of Circulating Maternal Steroid Concentrations in Third Trimester Pregnancies. III. Effect of Intravenous Cortisol Infusion on Maternal Concentrations of Estriol, 16α-Hydroxyprogesterone, 17α-Hydroxyprogesterone, Progesterone, 20α-Dihydroprogesterone, Δ⁵-Pregnenolone, Δ⁵-Pregnenolone Sulfate, Dehydroepiandrosterone Sulfate, and Cortisol

Elsner

Buster

Preston

et al. 1979

The Journal of Clinical Endocrinology & Metabolism

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The effect of a large dose (1000 mg) of iv cortisol-hemisuccinate on circulating steroid concentrations in five women, 28--34 weeks, gestational age, is reported. Maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol were measured by RIA before and at 8 and 12 h after iv cortisol infusions at 0 and 8 h. Data were evaluated by repeated measure analysis of variance. Estriol and 17 alpha-hydroxyprogesterone suppressed initially (P less than 0.05) and suppressed further with retreatment and increased treatment time (P less than 0.05). Dehydroepiandrosterone sulfate and progesterone suppressed initially (P less than 0.05) but did not suppress further with retreatment and increased treatment time (P greater than 0.05). delta 5-Pregnenolone and delta5-pregnenolone sulfate increased initially (P less than 0.05) but did not increase further (P greater than 0.05). Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1).

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Pregnenolone production in pregnancy

Cited by 13 publications

References 17 publications

Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-Chain Cleavage and 3β-Hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts

Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-Chain Cleavage and 3β-Hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts

Endocrine Disruption by Cadmium, a Common Environmental Toxicant with Paradoxical Effects on Reproduction

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