One of the most reliable findings in psychiatry is in the incidence of anxiety and depression. Beginning at puberty, women develop mood disorders twice as often as men. Because corticotropin-releasing factor (CRF) receptors are implicated, we compared CRF receptor binding in pre- and postpubertal rats. In each brain area, CRF receptor binding was sexually dimorphic, but no two areas were alike in the way the sexes differed. In the nucleus accumbens and olfactory tubercle, CRF1 binding was initially the same in juveniles, but became greater in adult females. In piriform cortex, CRF1 binding increased in females and decreased in males, again becoming sexually dimorphic. CRF1 binding in the anterior cingulate was greater in females than in males at both ages. In CA3, CRF1 binding was greater in males before puberty but decreased during puberty, abolishing the sex difference. CRF2 binding in the posterior bed nucleus of the stria terminalis was greater in males irrespective of age. In contrast, in each of three subdivisions of the lateral septum, females had greater CRF2 binding than males as juveniles, or, as juveniles and as adults. CRF2 binding in the ventromedial hypothalamus was the same in juveniles, but binding levels increased in males, leading to an adult sex difference. Thus, eight CRF receptor-expressing areas displayed eight distinct sex differences. These results show that sex differences pervade the CRF receptor system in juvenile and adult rats, and the mechanisms that control them are likely to be sex-, region-, and subtype-specific.

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