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).