2.4.1. Endogenous Opioid Peptides
Prepubescent rat pups do not exhibit significant sex differences in concentrations of beta-endorphin in the medulla, midbrain, diencephalon, telencephalon, hippocampus, striatum, cortex, and amygdala (Bayon et al., 1979). A lack of sex differences in beta-endorphin levels continues into adulthood in several key areas, including the median eminence, brainstem, parietal lobe, and the neurointermediate lobe of the pituitary (Petraglia et al., 1982; Pluchino et al., 2009). Sex differences emerge in some areas, with adult males exhibiting greater beta-endorphin concentrations in the prefrontal cortex than females, and with adult females exhibiting greater beta-endorphin concentrations in the hypothalamus, hippocampus and anterior pituitary than males (Pluchino et al., 2009; Wardlaw, 1986).
Similar to that reported for beta-endorphin, prepubescent rat pups do not exhibit sex differences in met/leu-enkephalin concentrations across many regions, including the medulla, midbrain, diencephalon, telencephalon, hippocampus, striatum, and amygdala (Bayon et al., 1979). Some significant sex differences emerge in adulthood, and these differences are region specific. For instance, adult females have greater concentrations of met-enkephalin immunoreactive fibers within the preoptic area (Watson et al, 1986) and greater concentrations of met- and leu-enkephalin in the cerebral cortex (Tang & Man, 1991) and leu-enkephalin in the CA3 region of the hippocampus (Van Kempen et al., 2013) than males. In contrast, adult males have significantly greater concentrations of met- and leu-enkephalin in the pituitary, including the anterior pituitary, than females (Hong, Yoshikawa, & Lamartinere, 1982; Yoshikawa & Hong, 1983; Tang & Man, 1991). These sex differences are due, in part, to gonadal hormones, given that both castration in males and ovariectomy in females reduces the magnitude of these differences (Yoshikawa & Hong, 1983). Finally, males have significantly more neurons containing proenkephalin mRNA within the anteroventral periventricular nucleus of the hypothalamus compared to females (Simerly, 1991).
A limited amount of data suggests sex differences in dynorphin concentrations across a few critical brain regions. For instance, males have higher concentrations of dynorphin in the anterior pituitary compared to females (Molineaux et al., 1986), whereas females have significantly more neurons containing prodynorphin mRNA in the anteroventral periventricular nucleus of the hypothalamus (Simerly, 1991), and greater dynorphin concentrations in the CA3 region of the hippocampus (Van Kempen et al., 2013) compared to males. There is also evidence that these sex differences are due in large part by the activity of gonadal hormones. For instance, females rats in diestrus and proestrus have significantly higher preprodynorphin mRNA levels within the spinal cord following injection of CFA relative to both male rats and female rats in estrus (Bradshaw et al, 2000). Moreover, ovariectomy increases preprodynorphin levels in the spinal cord relative to both intact and gonadectomized males, and castration significantly decreases preprodynorphin levels in the spinal cord of males (Bradshaw et al., 2000).