DOWN-REGULATION OF ANGIOTENSIN AT(1) RECEPTOR BY PROGESTERONE IN HUMAN PLACENTA

Regulation of the angiotensin AT(1) receptor in human placenta is poor ly understood. In this study, we analyzed the time course of angiotens in AT(1) receptor expression, internalization, and recycling by human trophoblast cells. We also studied the effects of estradiol, progester one, and chloroquine on regulation of the angiotensin AT(1) receptor i n 48-h cell culture. The angiotensin II receptor expression increased with the time of incubation, reaching a level at 48 h of culture that was about 120% above the initial value. A large majority of angiotensi n II receptors was of the AT(1) subtype, as it was completely inhibite d by losartan (1 mu mol/L). The internalization of [I-125]angiotensin II binding and the angiotensin AT(1) receptor recycling were also time dependent, with t1/2, values of 12 and 21 min, respectively. In human trophoblast cells exposed to progesterone (10 mu mol/L) for 48 h, ang iotensin AT(1) receptor density was decreased by 49%, whereas estradio l (10 mu mol/L) or chloroquine (100 mu mol/L) treatment was ineffectiv e. In the freshly isolated trophoblast cells initially treated with un labeled angiotensin II (200 nmol/L) for 30 min, chloroquine was shown to decrease angiotensin AT(1) receptor recycling by 73%, whereas estra diol and progesterone had no effect. These findings indicate that prog esterone induces a down-regulation of the angiotensin AT(1) receptor i n human placenta and that the recycling of this receptor can be delaye d by chloroquine.