Therapeutic effects of danazol on endometrial cells may be activated by the presence of extracellular matrix

Objective: To demonstrate the direct effect of danazol on the endometrium in the presence of various types of extracellular matrix. Study Design: Human endometrial cells (epithelial and stromal cells) were cultured over various extracellular matrix in the absence or presence of danazol. The effects of danazol on the growth of endometrial cells and the specific glandular structure were studied. Results: Danazol (10 −7 mol/L) inhibited endometrial cell growth, and in the presence of Matrigel, the same danazol concentration demonstrated a stronger inhibitory effect on epithelial cell growth. Danazol inhibited the formation of the specific glandular structure. Its effect depended on the culture substrates used and was reversible. Danazol did not inhibit growth of cells cultured over type V collagen substrate, whereas growth of those grown over type IV collagen was greatly inhibited. Conclusion: The results indicate that a distinctive extracellular matrix around ectopic endometriotic tissue modulates cell growth and differentiation. Endometrium associated with a normal extracellular matrix is apparently protected from therapeutic drugs, whereas endometriotic tissue growing over a deranged extracellular matrix would be sensitive to therapeutic drugs, such as danazol.