Distribution patterns of estrogen receptor α and β in the human cortex and hippocampus during development and adulthood

Abstract

The expression of estrogen receptors (ERs) in the developing and adult human brain has not been clearly established, although estrogens are crucial for neuronal differentiation, synapse formation, and cognitive functions. By using immunohistochemistry, we have studied the distribution of ER alpha and ER beta in human cerebral cortex and hippocampus from early prenatal stages to adult life. ER alpha was detected in the cortex at 9 gestational weeks (GW), with a high expression in proliferating zones and the cortical plate. The staining intensity decreased gradually during prenatal development but increased again from birth to adulthood. In contrast, ER beta was first detected at 15 GW in proliferating zones, and at 16/17 GW, numerous ER beta immunopositive cells were also observed in the cortical plate. ER beta expression persisted in the adult cortex, being widely distributed throughout cortical layers II-VI. In addition, from around 15 GW to adulthood, ER alpha and ER beta were expressed in human hippocampus mainly in pyramidal cells of Ammon's horn and in the dentate gyrus. Western blotting and immunohistochemistry in the adult cerebral cortex and hippocampus revealed lower protein expression of ER alpha compared with ER beta. Double immunostaining showed that during fetal life both ERs are expressed in neurons as well as in radial glia, although only ER alpha is expressed in the Cajal-Retzius neurons of the marginal zone. These observations demonstrate that the expression of ER alpha and ER beta displays different spatial-temporal patterns during human cortical and hippocampal development and suggest that both ERs may play distinct roles in several processes related to prenatal brain development.

Hormone levels and cognitive function in postmenopausal midlife women

“…Estrogen receptor beta shows a wide distribution within layer II-VI cortical neurons (González et al, 2007), providing a hypothetical link between menopausal estrogen loss and semantic memory symptoms. The association between estradiol and naming suggests the need to examine more closely the effects of menopause on this particular cognitive ability.…”

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

“…4 As estrogen has been thought to be involved in pathophysiology of psychiatric disorders, 5 we need to know its role during development. Despite these needs, very few attempts have been made to investigate lifetime dynamics of ERs in the central nervous system (CNS), [6][7][8][9] and we still cannot predict how the aging or diseased brain will respond to estrogen.…”

Estrogen Receptor Alpha Inhibits the Estrogen-Mediated Suppression of HIV Transcription in Astrocytes: Implications for Estrogen Neuroprotection in HIV Dementia

“…29 SVGA cells were derived from fetal human brain tissue isolated at 8-12 weeks gestation, a time when ERa expression in the cortex has started to decline, while expression in the hippocampus has yet to occur. 37,41 Together this suggests that the absence of detectable levels of ERa in SVGA cells may be because the cells are not fully differentiated into mature astrocytes. Indeed, SVGA cells have been described as a presumptive progenitor cell of the CNS that morphologically does not appear differentiated.…”

“…Peroxidase staining for ERa and GFAP was performed. 36,37 Sections were deparaffinized, boiled in CBS as before, and incubated in 0.3% hydrogen peroxide in TBS containing 0.3% Triton X-100 for 30 min. After rinsing in TBS, sections were blocked in 5% normal goat serum for 1 h at RT followed by incubation at RT overnight in rabbit anti-ERa (1:75 MC-20, Santa Cruz Biotech.…”