Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status

The present study reports the first systematic rostrocaudal distribution of estrogen receptor-alpha immunoreactivity (ERalpha-ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was investigated. In addition, three age-matched subjects with abnormal levels of estrogens were studied: a castrated, estrogen-treated 50-year-old male-to-female transsexual (T1), a 31-year-old man with an estrogen-producing tumor (S2), and an ovariectomized 46-year-old woman (S8). A strong sex difference, with more nuclear ERalpha-ir in women, was observed rostrally in the diagonal band of Broca and caudally in the medial mamillary nucleus. Less robust sex differences were observed in other brain areas, with more intense nuclear ERalpha-ir in men, e.g., in the sexually dimorphic nucleus of the medial preoptic area, paraventricular nucleus, and lateral hypothalamic area, whereas women had more nuclear ERalpha-ir in the suprachiasmatic nucleus and ventromedial nucleus. No nuclear sex differences in ERalpha were found, e.g., in the central part of the bed nucleus of the stria terminalis. In addition to nuclear staining, ERalpha-ir appeared to be sex-dependently present in the cytoplasm of neurons and was observed in astrocytes, plexus choroideus, and other non-neuronal cells. ERalpha-ir in T1, S2, and S8 suggested that most of the observed sex differences in ERalpha-ir are "activational" (e.g., ventromedial nucleus/medial mamillary nucleus) rather than "organizational." Species similarities and differences in ERalpha-ir distribution and possible functional implications are discussed.