title: Endocrine disruptors differently influence estrogen receptor β and androgen receptor in male and female rat VSMC.
abstract: Sex steroid hormones differently control the major physiological processes in male and female organisms. In particular, their effects on vascular smooth muscle cells (VSMCs) migration are at the root of sex/gender-related differences reported in the cardiovascular system. Several exogenous substances, defined endocrine disruptor chemicals (EDCs), could interfere with these androgen and estrogen effects; however, the sex/gender-related susceptibility of VSMC motility to EDCs is completely unknown. Here, the effect of naturally occurring (naringenin, Nar) and synthetic (bisphenol A, BPA) EDCs on male and female VSMC motility has been evaluated. 17β-estradiol (E2, 0.1 nM-1 µM) induced a dose-dependent inhibition of motility in female-derived VSMC. In contrast, neither dihydrotestosterone (DHT, 0.01-100 nM) nor the common precursor of sex steroid hormones, testosterone (Tes, 0.01-100 nM) modified male-derived VSMC motility. Estrogen receptor (ER) β subtype-dependent activation of p38 was necessary for the E2 effect on cell motility. High BPA concentration prevented E2 effects in female-derived cells being without any effect in male-derived cells. Nar mimicked E2 effects on female-derived cells even in the presence of E2 or BPA. Intriguingly, Nar also inhibited the male-derived VSMC mobility. This latter effect was prevented by ERβ inhibitor, but not by the androgen receptor (AR) inhibitor. As a whole, ERβ-dependent signals in VSMC results more susceptible to the impact of EDCs than AR signals suggesting a possible high and overall susceptibility of female to EDCs. However, several male-derived cells, including VSMC, express ERβ, which could also serve as target of EDC disruption in male organisms.
authors.affiliation: Department of Science, University Roma Tre, Roma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Pamela
authors.initials: P
authors.lastname: Bulzomi
authors.forename: Marco
authors.initials: M
authors.lastname: Lecis
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campesi
authors.forename: Flavia
authors.initials: F
authors.lastname: Franconi
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D047629:Estrogen Receptor beta; D044950:Flavanones; D010636:Phenols; D011944:Receptors, Androgen; C005273:naringenin; C006780:bisphenol A; D000098826:Bisphenol A Compounds