8-METHOXYPSORALEN SUPPRESSES PRODUCTION OF OVARIAN AROMATASE PROTEINS

• Published in: Toxin reviews 2005, Vol.24 (2), p.235-245
• Main Authors: McDermott, Danielle S., Hoyer, Patricia B., Diawara, Moussa M.
• Format: Article
• Language: English
• Subjects: 17-β estradiol; CYP19; Ovarian toxicity; psoralens; PUVA
• ISSN: 1556-9543; 1556-9551
• DOI: 10.1081/TXR-200057861

Abstract 8-Methoxypsoralen (8-MOP) is a natural plant biosynthetic metabolite found in produce. Its synthetic form is also widely used in combination with ultraviolet A irradiation in skin photochemotherapy, a procedure called psoralen ultraviolet A (PUVA). This compound has been implicated in a number of adverse reproductive effects in the Wistar rat, including decreased birth rate as a result of decreased ovulations, reduction in levels of circulating 17-β estradiol, and reduction in the granulosa cell population in antral ovarian follicles. The present study examines the potential for decreased production of aromatase (cytochrome P450 19) proteins in the ovaries as a mechanism of 8-MOP-mediated toxicity. Aromatase proteins were measured by Western blotting as a possible origin of decreased estradiol, and estradiol production was measured by radioimmunoassay. Significant decreases in both aromatase proteins and estradiol levels were observed. These results, which are also supported by a decrease in pituitary weight and, possibly, pituitary function, show the potential for 8-MOP-mediated infertility and may explain, in part, adverse reproductive effects reported in humans undergoing PUVA. The findings are consistent with previous observations and with the hypothesis that 8-MOP may affect reproductive function by adversely impacting organs in the hypothalamic-pituitary-gonadal axis.