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

This study reports the first systematic rostrocaudal distribution of estrogen receptor beta immunoreactivity (ERbeta-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 ERalpha in the same patients. ERbeta-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 ERbeta-ir in synaptic terminals, were additionally observed in various areas. Men showed more robust nuclear ERbeta-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, ERbeta-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 ERbeta-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 ERbeta expression. ERbeta-ir expression patterns in subjects with abnormal hormone levels suggests that there may be sex differences in ERbeta-ir that are "activational" rather than "organizational" in nature. Similarities, differences, potential functional, and clinical implications of the observed ERalpha and ERbeta distributions are discussed in relation to reproduction, autonomic-function, mood, cognition, and neuroprotection in health and disease. (C) 2003 Wiley-Liss, Inc.