Evaluation of Placental Steroids in Diabetic Pregnancy

Hertogh, R. De

doi:10.1007/978-3-642-66972-9_18

Cited by 5 publications

(1 citation statement)

References 58 publications

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“…The feto-placental unit is the major site of steroidogenesis in the pregnant woman but so far the possible role of growth factors in regulating placental steroidogenic enzymes has received little attention. One area of investigation in this field has arisen from the observation that pregnant diabetic women have lower serum oestrogen and higher progesterone levels than non-diabetic women (De Hertogh, 1979). This has led to an examination of the effect of insulin and IGF-I on aromatase and cholesterol SCC enzyme activities in cultured human placental cytotrophoblasts (Nestler & Williams, 1987).…”

Section: Placenta a N D Uterusmentioning

confidence: 99%

Regulation of Steroid Synthesis and Metabolism by Growth Factors

Reed

James

1989

Clinical Endocrinology

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Section: Placenta a N D Uterusmentioning

confidence: 99%

Regulation of Steroid Synthesis and Metabolism by Growth Factors

Reed

James

1989

Clinical Endocrinology

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Diabetes Mellitus and the Fetus

Gillmer

Oakley

Persson

1984

Fetal Physiology and Medicine

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Modulation of Aromatase and P450 Cholesterol Side-Chain Cleavage Enzyme Activities of Human Placental Cytotrophoblasts by Insulin and Insulin-Like Growth Factor I*

Nestler

1987

Endocrinology

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The placenta is the primary source of estrogens and progesterone during pregnancy. Because pregnant diabetic women are reported to have lower serum estrogen and higher progesterone concentrations than nondiabetic pregnant women, we studied the roles of insulin and insulin-like growth factor I (IGF-I) in the regulation of human cytotrophoblastic aromatase and P450 side-chain cleavage enzyme (P450 SCC) activities. Incubation of cytotrophoblasts with insulin or IGF-I for 24 h significantly inhibited the conversion of androstenedione to estrogens by approximately 20-40%. Insulin and IGF-I suppressed aromatization at doses as low as 20 and 10 ng/ml, respectively. Insulin's suppressive effect was demonstrable only after 18-22 h of incubation, suggesting an effect of insulin on aromatase protein mass rather than on aromatase activity. Cytotrophoblasts pretreated with insulin for 24 h possessed 23-30% less aromatase activity than control cells, as quantitated directly by the specific release of 3H2O from [3H]androstenedione, indicating that insulin inhibited estrogen synthesis rather than increased estrogen catabolism. Insulin's suppressive effect on aromatase was not due to a toxic effect of insulin, since incubates exposed to insulin for 24 h showed no decrease in cell number, cellular DNA content, or cellular protein content compared to control incubates. Also, insulin's suppression of aromatization was not due to increased cAMP phosphodiesterase activity, since cotreatment with 1 mM (Bu)2cAMP did not alter insulin's suppressive effect. Blockade of the IGF-I receptor of cytotrophoblasts with alpha IR-3, a monoclonal anti-IGF-I receptor antibody, prevented the suppression of aromatase activity by IGF-I, but did not alter insulin's inhibitory effect. This suggests that the two hormones inhibit aromatization via activation of their specific receptors and not by cross-association. Insulin treatment did not affect P450 SCC activity, whereas IGF-I treatment significantly stimulated P450 SCC activity by 19-36%, as measured by the conversion of 25-hydroxycholesterol to progesterone. These studies indicate that insulin exerts a selective inhibitory effect on cytotrophoblastic aromatase activity, whereas IGF-I inhibits aromatase activity but stimulates P450 SCC activity. Since pregnant diabetic women manifest peripheral hyperinsulinemia, and IGF-I levels in fetal cord sera from diabetic pregnancies are elevated, these observations may help explain the lower serum estrogen and elevated progesterone levels associated with diabetic pregnancy.

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Evaluation of Placental Steroids in Diabetic Pregnancy

Cited by 5 publications

References 58 publications

Regulation of Steroid Synthesis and Metabolism by Growth Factors

Regulation of Steroid Synthesis and Metabolism by Growth Factors

Diabetes Mellitus and the Fetus

Modulation of Aromatase and P450 Cholesterol Side-Chain Cleavage Enzyme Activities of Human Placental Cytotrophoblasts by Insulin and Insulin-Like Growth Factor I*

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