Estrogen-receptor-beta distribution in the human hypothalamus: similarities and differences with ER alpha distribution.

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.