Tyrosine kinase activity of insulin-like growth factor I and insulin receptors in human endometrium during the menstrual cycle: cyclic variation of insulin receptor expression.

OBJECTIVE

To determine whether expression and binding or signaling characteristics of endometrial insulin-like growth factor I (IGF-I) and insulin receptors are modulated throughout the menstrual cycle.

SETTING

Research laboratories of a university hospital and of the Institute for Diabetes Research.

DESIGN

In vitro receptor binding and phosphorylation studies of human proliferative and secretory endometrial tissue and of cultured endometrial stromal cells.

MAIN OUTCOME MEASURES

Binding and tyrosine kinase activation of IGF-I and insulin were studied in wheat germ agglutinin purified receptor protein. Binding data were analyzed by Scatchard plots. Autophosphorylation was measured by 32P incorporation into the 95 kd receptor beta-subunit; substrate phosphorylation was determined with poly(GluNa 4: Tyr 1).

RESULTS

Binding studies revealed no differences of the affinities between cycle phases. Half-maximal displacement of both receptors was approximately 1 nM in both phases. Insulin-like growth factor I receptor number appeared to be unaltered in both phases, whereas insulin receptor numbers and tyrosine kinase activity in the secretory phase were significantly increased. The increase of tyrosine kinase activity was entirely because of the increased receptor number as calculated from the binding data. In cultured endometrial stromal cells the increase of expression of insulin receptors could be induced by sexual steroids.

CONCLUSIONS

On the receptor level IGF-I signaling to human endometrium is not modulated during the menstrual cycle, whereas insulin binding and signaling are likely to be enhanced in the luteal phase. The increased insulin receptor level may be required for normal luteal function.