Sex Differences in Genital Area Hyperpigmentation Induced by 5-Fluorouracil Administration in Mice

Area of Science:

• Pharmacology
• Oncology
• Endocrinology

Background:

• Anticancer drugs like 5-fluorouracil (5-FU) can cause skin pigmentation, impacting quality of life.
• Previous research linked 5-FU-induced pigmentation to increased adrenocorticotropic hormone (ACTH) and reactive oxygen species (ROS).

Purpose of the Study:

• To investigate the sex-based differences in 5-FU-induced hyperpigmentation.
• To explore the underlying mechanisms, including hormonal and inflammatory factors, contributing to these sex differences.

Main Methods:

• Administration of 5-FU to male and female Hos:HRM-2 mice.
• Monitoring for pigmentation, and measuring levels of neutrophils, ACTH, ROS, noradrenaline, and estradiol.
• Analyzing the relationship between these factors and the development of hyperpigmentation.

Main Results:

• Male mice developed genital pigmentation with elevated neutrophils, ACTH, and ROS.
• Female mice showed increased neutrophils and noradrenaline, but not ACTH or ROS, and did not develop pigmentation.
• Estradiol levels decreased significantly in female mice, potentially suppressing ROS production and enhancing neutrophil apoptosis.

Conclusions:

• Sex differences in 5-FU-induced hyperpigmentation are evident.
• Fluctuations in estradiol, alongside changes in neutrophils, ROS, and ACTH, likely mediate these sex differences.
• The interplay between the hypothalamus-pituitary-adrenal axis and sex hormones may explain the observed phenomenon.