The role of estrogen as a parahormone in brain and pituitary

Where aromatase and estrogen receptors are co-localized in brain and pituitary, estrogen functions as a parahormone, and estrogen levels which determine the occurrence or magnitude of a response are those in close proximity to targets. Teleost fish, a vertebrate group characterized by exceptionally high aromatase in neuroendocrine tissues, are technically advantageous animal models for studying the cellular location of aromatase, natural changes correlated with seasonal reproductive cycles, substrate-dependence of the reaction, steroid induction of enzyme activity, and possible non-genomic actions of estrogen on cultured neurons. In addition, characterization of steroid receptors reveals that the androgen receptor, like aromatase, is present in unusually high concentrations (10- to 100-fold higher than in mammalian brain). Since androgen receptors and aromatase both utilize testosterone as a ligand, their high abundance in teleost brain may be the consequence of a functional interdependence during evolution, although the primary causal factor is unknown. These studies illustrate the usefulness of unconventional species and a comparative approach for obtaining new insights into brain-steroid interactions.