Therapeutic effects of melatonin in female mice with central precocious puberty by regulating the hypothalamic Kiss-1/Kiss1R system.
Level 5 - mechanism / opinion, no new human data
Animal model study (preclinical research)
PubMed 38029845 · doi:10.1016/j.bbr.2023.114783
What was done
Researchers established a central precocious puberty (CPP) model in female mice via subcutaneous injection of 300 µg danazol at postnatal day 5. Mice received treatment with melatonin or leuprolide. The study monitored time to vaginal opening, body weight, gonadal weight, gonadal index, and reproductive tract histology (H&E staining). Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured by ELISA. Hypothalamic expression of Kiss-1, Kiss-1 receptor (Kiss1R), and gonadotropin-releasing hormone (GnRH), alongside pituitary GnRH receptor (GnRHR), were measured using RT-PCR and Western blotting.
What was found
Melatonin delayed the timing of vaginal opening, decreased body weight, gonadal weight, and gonadal indices, and prevented uterine wall thickening and ovarian luteinization in CPP mice. It also reduced serum concentrations of FSH, LH, and E2. Furthermore, melatonin suppressed mRNA and protein expression of hypothalamic Kiss-1, Kiss1R, and GnRH, as well as pituitary GnRHR. The abstract did not report exact numerical values, effect sizes, or p-values.
Why it matters
This study provides preclinical mechanistic evidence that melatonin can suppress the hypothalamic-pituitary-gonadal axis in female mice by downregulating the Kiss-1/Kiss1R pathway, indicating a potential regulatory mechanism relevant to central precocious puberty.
Limits
The study was conducted entirely in a chemically induced rodent model, which may not capture the clinical complexity of human central precocious puberty. The abstract does not disclose the total sample size (n), dosing regimens, duration of melatonin treatment, or quantitative data with variance estimates. Clinical efficacy and safety in children cannot be inferred.
Cited by
- supports High doses of supplemental melatonin suppress the hypothalamic-pituitary-gonadal axis and can delay puberty in animal studies.