Estrogen‐receptor‐β distribution in the human hypothalamus: Similarities and differences with ERα distribution

Abstract

This study reports the first systematic rostrocaudal distribution of estrogen receptor beta immunoreactivity (ER beta-ir) in the human hypothalamus and adjacent areas in five males and five females between 20-39 years of age and compares its distribution to previously reported ER alpha in the same patients. ER beta-ir was generally observed more frequently in the cytoplasm than in the nucleus and appeared to be stronger in women. Basket-like fiber stainings, suggestive for ER beta-ir in synaptic terminals, were additionally observed in various areas. Men showed more robust nuclear ER beta-ir than women in the medial part of the bed nucleus of the stria terminalis, paraventricular and paratenial nucleus of the thalamus, while less intense, but more nuclear, ER beta-ir appeared to be present in, e.g., the BSTc, sexually dimorphic nucleus of the medial preoptic area, diagonal band of Broca and ventromedial nucleus. Women revealed more nuclear ER beta-ir than men of a low to intermediate level, e.g., in the suprachiasmatic, supraoptic, paraventricular, infundibular, and medial mamillary nucleus. These data indicate potential sex differences in ER beta expression. ER beta-ir expression patterns in subjects with abnormal hormone levels suggests that there may be sex differences in ER beta-ir that are "activational" rather than "organizational" in nature. Similarities, differences, potential functional, and clinical implications of the observed ER alpha and ER beta distributions are discussed in relation to reproduction, autonomic-function, mood, cognition, and neuroprotection in health and disease.

Increased estrogen receptor β expression correlates with decreased spine formation in the rat hippocampus

“…This is supported by recent ultrastructural studies (Milner et al, 2005). Notably, these ERb compartmentalization findings hold true for the human hippocampus (Savaskan et al, 2001;Lu et al, 2004), as well as the hypothalamus (Ishunina et al, 2000;Kruijver et al, 2002Kruijver et al, , 2003.…”

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

“…Women showed more nuclear ERβ staining in the SCN, the SON, the PVN, the INF and the MMN (75). Observations in subjects with abnormal hormone levels showed, in most areas, ERβ immunoreactivity distribution patterns that were consistent with the level of circulating estrogens, suggesting that the majority of the reported sex differences in ERβ immunoreactivity are "activational" rather than "organizational" in nature (76,77). In the BSTc, differences in sex hormone receptors such as ERα, ERβ, the AR and progesterone receptor (PR), are present from fetal age onward.…”

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

“…These include regions of human and animal brains that are important for cognition, memory, and affect, such as the hippocampus, amygdala, and cortex (Kelly et al, 1999;BaronCohen et al, 2005;McCarthy and Konkle, 2005;Cahill, 2006;Cosgrove et al, 2007;Wilson and Davies, 2007), and for regions controlling sensorimotor and reward systems (Becker, 1999;Dewing et al, 2006;Cantuti-Castelvetri et al, 2007;McArthur et al, 2007a). Indeed, post mortem studies, as well as evidence from new technologies for in vivo imaging, are adding rapidly to the view that sex differences in the human brain may be the norm rather than the exception (Madeira and Lieberman, 1995;Allen et al, 2003;Kruijver et al, 2003;Luders et al, 2004;Mechelli et al, 2005;Cosgrove et al, 2007;Ishunina and Swaab, 2008;Swaab, 2008).…”