Corticotropin-Releasing Factor Receptor Binding in the Amygdala Changes Across Puberty in a Sex-Specific Manner

Corticotropin-releasing factor receptors type 1 (CRF1) and type 2 (CRF2) have complementary roles in controlling the hypothalamic-pituitary-adrenal (HPA) axis. Because CRF receptors are expressed in sex steroid-sensitive areas of the forebrain, they may contribute to sex-specific patterns of stress sensitivity and susceptibility to stress-related mood disorders, which are more frequent in women. To determine whether CRF receptors vary as a function of age and/or sex, we measured receptor binding in the amygdala of male and female, prepubertal and adult rats. Both receptor subtypes demonstrated age- and sex-specific binding patterns. In the basolateral amygdala and posteroventral medial amygdala, CRF1 binding decreased in males and increased in females after puberty, there, CRF2 binding increased in males and was unchanged in females. In the posterodorsal medial amygdala, CRF1 binding was unchanged across puberty, whereas CRF2 binding increased across puberty far more in males than in females. Binding was lowest overall in the central amygdala; there, CRF1 was unchanged while CRF2 binding increased across puberty only in males. Thus, in all four examined areas across prepuberty to adulthood, CRF2 binding increased far more in males than in females and resulted in significantly more binding in adult males than in adult females. These sex-specific developmental patterns are consistent with sex differences in hypothalamic-pituitary-adrenal responsiveness and may thus contribute to sex differences in mood disorder susceptibility.