Estrogen receptor-alpha immunoreactive neurons in the brainstem and spinal cord of the female rhesus monkey: species-specific characteristics.

The distribution pattern of estrogen receptors in the rodent CNS has been reported extensively, but mapping of estrogen receptors in primates is incomplete. In this study we describe the distribution of estrogen receptor alpha immunoreactive (ER-alpha IR) neurons in the brainstem and spinal cord of the rhesus monkey. In the midbrain, ER-alpha IR neurons were located in the periaqueductal gray, especially the caudal ventrolateral part, the adjacent tegmentum, peripeduncular nucleus, and pretectal nucleus. A few ER-alpha IR neurons were found in the lateral parabrachial nucleus, lateral pontine tegmentum, and pontine gray medial to the locus coeruleus. At caudal medullary levels, ER-alpha IR neurons were present in the commissural nucleus of the solitary complex and the caudal spinal trigeminal nucleus. The remaining regions of the brainstem were devoid of ER-alpha IR neurons. Spinal ER-alpha IR neurons were found in laminae I-V, and area X, and were most numerous in lower lumbar and sacral segments. The lateral collateral pathway and dorsal commissural nuclei of the sacral cord and the thoracic intermediolateral cell column also contained ER-alpha IR neurons. Estrogen treatment did not result in any differences in the distribution pattern of ER-alpha IR neurons. The results indicate that ER-alpha IR neurons in the primate brainstem and spinal cord are concentrated mainly in regions involved in sensory and autonomic processing. Compared with rodent species, the regional distribution of ER-alpha IR neurons is less widespread, and ER-alpha IR neurons in regions such as the spinal dorsal horn and caudal spinal trigeminal nucleus appear to be less abundant. These distinctions suggest a modest role of ER-alpha in estrogen-mediated actions on primate brainstem and spinal systems. These differences may contribute to variations in behavioral effects of estrogen between primate and rodent species.

Projections from estrogen receptor-alpha immunoreactive neurons in the periaqueductal gray to the lateral medulla oblongata in the rhesus monkey.

The periaqueductal gray (PAG) contains numerous estrogen receptor-alpha immunoreactive (ER-alpha IR) neurons that are distributed in a species-specific way. These neurons might modulate different types of behavior that are mediated by the PAG such as active and passive coping responses, analgesia, and reproductive behavior. In primates, it is not known whether ER-alpha IR PAG neurons represent local interneurons and/or neurons that project to brainstem areas that control these behaviors. In this double labeling study, we asked whether ER-alpha IR neurons in the PAG of the rhesus monkey project to the nucleus retroambiguus (NRA), an area in the ventrolateral caudal medulla oblongata that is involved in expiration, vocalization, and reproductive behavior. Tracer was injected into the caudal lateral medulla oblongata to retrogradely label PAG neurons, and ER-alpha was visualized immunohistochemically. Although ER-alpha IR neurons and NRA-projection neurons were present at similar levels of the PAG, their distributions hardly overlapped. ER-alpha IR PAG neurons that project to the lateral caudal medulla represented less than 2% of ER-alpha IR PAG neurons. These double-labeled neurons were mainly located in the ipsilateral caudal PAG. The cluster of neurons in the medial part of the lateral PAG that projects specifically to the NRA-region did not contain double-labeled cells. The results indicate that only a few ER-alpha IR PAG neurons project to the NRA-region. This might be related to the modest effects of estrogen on mating-related behavior in primates compared most other mammalian species. Remaining ER-alpha IR PAG neurons might act locally on other PAG neurons, or they might represent neurons that project to other areas. Furthermore, the finding that the distributions of ER-alpha IR neurons and neurons that project to premotor neurons in the NRA-region scarcely overlap illustrates that the PAG in primates is very highly organized into anatomically distinct regions compared with other species.