Review: Puberty as a time of remodeling the adult response to ovarian hormones

•Some peripubertal stressors alter behavioral response to estradiol and progesterone in adulthood.•Pubertal shipping or immune challenge remodel the brain’s behavioral response to estradiol and progesterone.•The authors propose that mice may be a model for studying the etiology of some types of hormone-influenced mental illness in women. During pubertal development, an animal’s response to stress changes and sexual differentiation of the brain and behavior continue. We discovered that particular stressors, such as shipping from suppliers or an immune challenge with lipopolysaccharide, during the prolonged pubertal period of female mice result in long-term changes in behavioral responsiveness of the brain to estradiol assessed in adulthood. All behaviors influenced by estradiol and/or progesterone that we have studied are compromised by a stressor during pubertal development. Depending on the behavior, immune challenge or shipping from suppliers during pubertal development decreases, eliminates, or even reverses the effects of estradiol. Shipping during this period causes changes in the number of estrogen receptor-immunoreactive cells in key brain areas suggesting one cellular mechanism for this remodeling of the brain’s response to hormones. We suggest that particular adverse experiences in girls may cause long-term alterations in the brain’s response to estradiol and/or progesterone via activation of the immune system. This in turn could lead to an alteration in any aspect of mental health that is influenced by estradiol.