Effect of phytoestrogens on basal and GnRH-induced gonadotropin secretion

Plant-derived estrogens (phytoestrogens, PEs), like endogenous estrogens, affect a diverse array of tissues, including the bone, uterus, mammary gland, and components of the neural andcardiovascularsystems.WehypothesizedthatPEsactdirectlyatpituitarylocitoattenuate basalFSHsecretionandincreasegonadotropesensitivitytoGnRH.ToexaminetheeffectofPEs on basal secretion and total production of FSH, ovine pituitary cells were incubated with PEs for48 h. Conditioned media and cell extractwere collected and assayedfor FSH. Estradiol (E2) andsomePEssignificantlydecreasedbasalsecretionofFSH.ThemostpotentPEsinthisregard were coumestrol (CM), zearalenone (ZR), and genistein (GN). The specificity of PE-induced suppressionofbasalFSHwasindicatedbytheabsenceofsuppressionincellscoincubatedwith PEsandanestrogenreceptor(ER)blocker (ICI182 780;ICI).SecretionofLHduringstimulation by a GnRH agonist (GnRH-A) was used as a measure of gonadotrope responsiveness. Incubation of cells for 12 h with E2, CM, ZR, GN, or daidzein (DZ) enhanced the magnitude and sensitivity of LH secretion during subsequent exposure to graded levels of a GnRH-A. The E2-andPE-dependentaugmentationofgonadotroperesponsivenesswasnearlyfullyblocked during coincubation with ICI. Collectively, these data demonstrate that selected PEs (CM, ZR, and GN), like E2, decrease basal secretion of FSH, reduce total FSH production, and enhance GnRH-A-induced LH secretion in a manner that is dependent on the ER.