REGULATION OF THE AROMATASE-ACTIVITY OF HUMAN PLACENTAL CYTOTROPHOBLASTS BY INSULIN, INSULIN-LIKE GROWTH FACTOR-I, AND FACTOR-II

Studies to be reviewed were stimulated by the clinical observation, al beit controversial, that diabetic pregnancy may be associated with low er serum oestrogen levels than nondiabetic pregnancy. Pregnant diabeti c women are usually intensively treated with insulin to maintain eugly cemia, frequently resulting in peripheral hyperinsulinemia. The placen ta, which is the primary source of oestrogens during pregnancy, would be exposed to this elevation in circulating insulin levels. Similarly, insulin-like growth factors (IGFs), which are synthesized and secrete d by placental tissues and could influence placental function in an au tocrine or paracrine fashion, may be elevated in diabetic pregnancy. W e will review studies, which show that (i) insulin, insulin-like growt h factor-I (IGF-I), and -II inhibit the aromatase activity of human cy totrophoblasts, (ii) these peptides can inhibit aromatase by activatio n of their respective receptors, and (iii) the potency of IGF-II in su ppressing aromatase greatly exceeds that of either insulin or IGF-I. F inally, evidence will be reviewed, which suggests that inositolglycan mediators ('second messengers') serve as the signal transduction syste m for insulin's inhibition of aromatase activity. Hence, placental exp osure to increased concentrations of insulin and/or IGFs in the pregna nt diabetic woman may result in inhibition of aromatase activity and d ecreased serum oestrogen levels.