Selective colocalization of immunoreactivity for intracellular gonadal hormone receptors and tyrosine hydroxylase in the ventral tegmental area, substantia nigra, and retrorubral fields in the rat

Gonadal hormones influence brain functions, including motor and motivational behaviors, transmitter release, and receptor binding in midbrain dopamine systems. Much of this influence suggests genomic hormone action. To identify which midbrain cells may be targets of genomic influence, double label immunocytochemistry was used to map intracellular estrogen and androgen receptors and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA), substantia nigra (SN), and retrorubral fields (RRF) in intact, adult rats. The distribution of estrogen and androgen receptor immunoreactivity was highly selective, similar in males and females, and largely nonoverlapping. Estrogen receptors were present within subpopulations of cells in the ventrolateral paranigral VTA and rostrolateral RRF; of these, only a few cells in the RRF were immunoreactive for TH. Cells immunoreactive for androgen receptors were numerous in the paranigral and parabrachial VTA, SN pars lateralis and dorsomedial pars compacta, and lateral RRF. Nearly every androgen receptor-bearing cell in the VTA and SN pars compacta, roughly half in the SN pars lateralis, and about one-third in the RRF were TH immunopositive. The localization of estrogen receptors approximates the distribution of subsets of cells labeled following neostriatal injections, whereas androgen receptors tend to occupy regions labeled by injections in cortical or limbic targets. These receptor-specific alignments with origins of nigrostriatal, mesolimbic, and mesocortical projections are consistent with identified estrogen influence over motor behaviors and androgen involvement in motivational functions and may hold clues for understanding hormone action in these and other functions and dysfunctions of midbrain dopamine systems.