Hormone effects of zearalenone in nonhuman primates

Abstract

The ability of exogenous estrogens to alter serum levels of gonadotropins in ovariectomized rhesus monkeys was investigated in an attempt to develop a nonhuman primate model that could accurately predict both effective levels and physiologic consequences of human estrogen exposure. The ability of zearalenone (Z) and diethylstilbestrol (DES) to induce either a depression or an elevation of luteinizing hormone (LH) or follicle‐stimulating hormone (FSH) concentrations was compared to that of estradiol‐17β (E₂). E₂ administration initially caused a reduction of gonadotropin levels (3–15 hr after injection) followed by an LH but not always an FSH surge (36–72 hr after injection). Injection of DES and Z induced similar gonadotropin patterns. The ovariectomized rhesus monkey model was used to compare the oral and parenteral potencies of Z, DES, and E₂. The minimal doses of Z, DES, and E₂ that depressed LH levels after subcutaneous injection were 14, 0.5, and 4 μg/kg, respectively. When given orally, doses of 400, 2.5, and 5 μg/kg of Z, DES, and E₂ were needed to induce a significant decline in LH concentrations. FSH levels were depressed by injection of 56, 2, and 1 μg/kg of Z, DES, and E₂, respectively. Additional experiments were conducted to determine whether DES or Z would interfere with either the E₂‐induced gonadotropin depression or the subsequent gonadotropin peak. Since progesterone has been shown to block the estrogen‐induced LH surge but not to affect the LH depression, it was included as a positive control. As expected, progesterone blocked the induction of LH peaks by estradiol benzoate injection (40 μg/kg). Neither Z nor DES affected the LH peak or the depression.