Progesterone inhibits folic acid transport in human trophoblasts

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Elisa Keating (Author) Other; Gonçalves P (Author) FMUP; Lemos, C (Author) Other; Costa, F (Author) Other; Campos, I (Author) Other; Smith, SB (Author) Other; Bridges, CC (Author) Other; Martel, F (Author) FMUP

Journal

Title: Journal of Membrane Biology

Vol. 216

Pages: 143-152

ISSN: 0022-2631

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 27 Citations

Other information

Authenticus ID: P-004-AYY

DOI: 10.1007/s00232-007-9057-5

Abstract (EN): The aim of this work was to test the putative involvement of members of the ABC superfamily of transporters on folic acid (FA) cellular homeostasis in the human placenta. [H-3]FA uptake and efflux in BeWo cells were unaffected or hardly affected by multidrug resistance 1 (MDR1) inhibition (with verapamil), multidrug resistance protein (MRP) inhibition (with probenecid) or breast cancer resistance protein (BCRP) inhibition (with fumitremorgin C). However, [H-3]FA uptake and efflux were inhibited by progesterone (200 mu M). An inhibitory effect of progesterone upon [H-3]FA uptake and efflux was also observed in human cytotrophoblasts. Moreover, verapamil and ss-estradiol also reduced [H-3]FA efflux in these cells. Inhibition of [H-3]FA uptake in BeWo cells by progesterone seemed to be very specific since other tested steroids (beta-estradiol, corticosterone, testosterone, aldosterone, estrone and pregnanediol) were devoid of effect. However, efflux was also inhibited by beta-estradiol and corticosterone and stimulated by estrone. Moreover, the effect of progesterone upon the uptake of [H-3]FA by BeWo cells was concentration-dependent (IC50 = 65 [range 9-448] mu M) and seems to involve competitive inhibition. Also, progesterone (1-400 mu M) did not affect either [H-3]FA uptake or efflux at an external acidic pH. Finally, inhibition of [H-3]FA uptake by progesterone was unaffected by either 4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid (SITS), a known inhibitor of the reduced folate carrier (RFC), or an anti-RFC antibody. These results suggest that progesterone inhibits RFC. In conclusion, our results show that progesterone, a sterol produced by the placenta, inhibits both FA uptake and efflux in BeWo cells and primary cultured human trophoblasts.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10