MELATONIN INHIBITS MAMMARY-GLAND DEVELOPMENT IN FEMALE MICE

The objective of this study was to determine whether melatonin (aMT) influences the postnatal development of the mammary gland parenchyma in female mice from the time of weaning to adulthood. Twenty-one-day-old female BALBc mice were treated with daily subcutaneous injections of aMT (200 mug) or diluent, 3 hr before the onset of darkness (photoperiod LD 12:12). At 3, 5, 7, 9, 11, and 13 weeks of age, batches of 20 animals (ten controls and ten aMT-treated) were sacrificed and the second pair of mammary glands were dissected to evaluate their degree of development. Melatonin decreased body weight gain from 2 weeks before until 2 weeks after the onset of puberty. Treatment with aMT also resulted in a lower DNA content and smaller area of the mammary gland from the time of puberty until the end of the study. In aMT-treated mice the phase of highly positive allometric growth began 2 weeks later, but ended at the same time as in controls (11th week of life). Finally, aMT decreased the development of terminal, lateral, and alveolar buds while it increased the number of terminal ducts per gland. We conclude that pharmacological doses of aMT (1) reduce body weight gain at the peripuberal age; (2) partially inhibit postnatal mammary gland development by reducing the number of epithelial structures representing sites of growth and increasing that of structures representing the final state of ductal growth in virgin animals; (3) delay the onset of and shorten the phase of rapid mammary growth occurring in early postpuberal age.