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

Abstract

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.

Keywords: Anxiety; Cognitive function; Depression; Estradiol; Females; Immune challenge; Lipopolysaccharide; Mood disorders; Progesterone; Puberty; Sexual behavior; Stress.

Figure 1

Shipping female mice during pubertal development decreases sex behavioral response to estradiol and progesterone in adulthood. Lordosis quotient (LQ) (mean ± SEM) of C57Bl/6 female mice shipped during or after the peripubertal period. (*, p < 0.05). Reprinted from (16) Copyright 2009, The Endocrine Society.

Figure 2

Injection of LPS during pubertal development decreases sex behavioral response to estradiol and progesterone in adulthood. Lordosis quotient (LQ) (mean ± SEM) of C57Bl/6 female mice injected with 1.5 mg/kg LPS at 6 wk old. The lower x-axis refers to the animal's age at time of testing. (*= P < 0.05). Reprinted from (15) Copyright 2009, The Endocrine Society.

Figure 3

Shipping CD1 strain female mice during pubertal development decreases sex behavioral response to estradiol and progesterone in adulthood. Lordosis quotient (Mean±SEM) on fifth weely test of mice shipped at 3, 4, 6, 8 or 10 weeks. * = p < .05, significantly lower than females shipped at 3, 4 or 10 weeks old. Modified from (18)

Figure 4

Shipping female mice during pubertal development alters corticosterone levels in response to sex behavioral testing in adulthood. Corticosterone levels (mean ± SEM.) in serum taken 15 - 20 minutes in five weekly tests after start of female sexual behavior testing in female mice shipped at 6 weeks or 12 weeks (* = P < 0.01). Reprinted from (16) Copyright 2009, The Endocrine Society.

Figure 5

Shipping female mice during pubertal development results in reduction of ER-α levels in adulthood in some brain areas. Number of ER-α IR cells (mean ± SEM) in CD-1 female mice shipped at 4 or 6 weeks old in the arcuate nucleus (Arc), anteroventral paraventricular nucleus (AVPV), medial preoptic area (MPOA) and ventromedial nucleus of the hypothalamus (VMN). (*= p < 0.05) Reprinted from (18;18) with permission of Elsevier, Copyright 2011.

Figure 6

Estradiol increases the percentage of time spent investigating novel object during the object recognition test in mice treated peripubertally with saline, but not LPS. (Mean ± SEM; *p<0.05) Reprinted from (32) with permission from Elsevier, Inc.