Estrogen formation and binding in the cerebral cortex of the developing rhesus monkey.

Abstract

These studies were undertaken to determine whether estrogen receptors and the microsomal enzyme system called the aromatase complex, which is responsible for conversion of androgen to estrogen, are present in the brain of the rhesus monkey during perinatal life. Four monkeys (three females-one fetus removed on day 153 of gestation and two infants, 5 and 6 days postnatal-and 1 male, 2 days postnatal) were studied. Cytosol estrogen receptors were detected in all brain regions examined. The apparent equilibrium dissociations constants for reaction of these sites with [3H]moxestrol were similar to those for uterine and pituitary cytosol estrogen receptors (0.3-1.1 nM). Within the brain, highest levels of binding were observed in the hypothalamus-preoptic area, with fairly even, lower concentrations throughout the cortical structures. Aromatase complex activity was detected in the majority of the tissue specimens. The highest levels of estrogen formation were observed in the hypothalamus. However, the amygdala, the hippocampus, and several of the cortex samples also contained measurable aromatase complex activity. Among the cortical samples, the highest levels of aromatase complex activity were found in regions of the association cortex (the dorsolateral-prefrontal, orbital-prefrontal, anterior cingulate, and parietal cortices). The lowest levels of aromatase activity were found in the somatosensory and motor cortices of the postnatal animals. These results suggest that locally-formed estrogen may be involved in the effects of circulating androgens on the developing primate neocortex.In many mammals, sexual differentiation of the brain results primarily from sex differences in gonadal steroid hormone secretion during early life (1). Virtually all of the information about effects of gonadal steroids on the developing nervous system pertains to differentiation of diencephalic structures that underlie gender differences in gonadotrophin release and reproductive behavior. Evidence for direct effects of the gonadal hormones on the maturation of other brain structures is much more limited (2) and has never been reported for primates. There is, however, abundant behavioral evidence for sex differences in cerebral function in both humans and nonhuman primates. In the rhesus monkey (Macaca mulatta), sex differences have been reported in play behavior and in the effects of neocortical lesions during the first 3 months of postnatal life (3-6). In humans, sex differences have been reported in cognitive abilities, cerebral lateralization, play behavior, and incidence of a variety of childhood learning disorders (7-11). Circulating androgen levels during early life have been implicated as a possible causative factor for at least some of these sexual dimorphisms (11,12).In many subprimate mammalian species, local estrogen biosynthesis is believed to be critically important for androgen-induced sexual differentiation of the brain (1,13). The present studies demonstrate that estrogen receptors and the microsomal enzyme system...

Brain is the major site of estrogen synthesis in a male songbird.

“…This system undergoes striking morphological and functional changes during sexual differentiation and song learning, two processes that are regulated by estrogen (29,30). Estrogen has clear neurotrophic actions (31), and brain synthesis ofestrogen is spatially and temporally correlated with neural plasticity in diverse vertebrate species (4,32). Our data also suggest that rather than relying on estrogens from the periphery, the adult songbird brain itself provides the estrogens required for estrogenic regulation of neural plasticity in the song system.…”

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

“…This conclusion is strengthened by the finding of a very similar effect on vmPFC predominantly in males as a consequence of genetic variation of 5-HTTLPR, an autosomal gene. 26,27 Further research is necessary to clarify the cellular mechanisms underlying these observations; of note, sex hormone receptors are prominently expressed in amygdala, cingulate and orbitofrontal cortex, 67 where they are able to influence monoamine metabolism by regulating MAOA messenger RNA transcription. 68 One important aspect of this study is our finding that TPQ-assessed human temperament covaries with connectivity in a critical circuit for emotional arousal and regulation in MAOA-L males.…”

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

“…In the hypothalamus, electron microscopy imaging has demonstrated a synaptic localization for aromatase in avian, mammalian, and human tissue (Naftolin et al, 1971a,b;Callard et al, 1978;MacLusky et al, 1986;Naftolin et al, 1996;Yague et al, 2006Yague et al, , 2008Srivastava et al, 2010;Remage-Healey et al, 2011). Biochemical studies using subcellular preparations of brain tissue have detected high levels of aromatase activity in isolated presynaptic tissue preparations (Mak et al, 1985;Schlinger and Callard, 1989;Peterson et al, 2005;Remage-Healey et al, 2011), indicating a potential role of estrogens at synapses.…”

“…Aromatase enzyme activity has been described in several brain regions and cell types in vertebrate brains ranging from fish to humans (Naftolin et al, 1971a,b;Callard et al, 1978;MacLusky et al, 1986). Changes in aromatase activity can occur in a matter of minutes.…”