Although PZ also has been shown to display possible estrogenic, antiestrogenic, or aryl hydrocarbon receptor (AHR)-mediated effects in vitro, it is not certain whether PZ displays these endocrine activities in the whole animal. Furthermore, exposure to chemicals that disrupt female rat sexual differentiation by acting as estrogen or AHR agonists produce reproductive tract malformations that were not present in the PZ-treated female offspring.
In vitro, PZ acts like estrogen to reduce Esrl (estrogen receptor alpha [ERa] mRNA) and Esr2 (ERp mRNA) expression, as well as cause a transient reduction in ESR1 (ERa protein) expression in MCF7-BUS cells. In contrast, PZ also inhibited estrogen-induced responses in cell proliferation and ESR1 transactivation assays. Whether PZ could act as an estrogen agonist or antagonist could not be evaluated in the current study for several reasons. The fetal female reproductive tract will differentiate normally in the absence of ovaries or adrenal glands. Furthermore, mice lacking ESR1 or ESR2 develop a properly differentiated reproductive tract. Tests of estrogen responsiveness on adult or pubertal female reproductive tissues would be necessary to assess whether PZ has estrogen agonist or antagonist activity in vivo.