Estrogen receptor‐α and ‐β immunoreactive neurons in the brainstem and spinal cord of male and female mice: Relationships to monoaminergic, cholinergic, and spinal projection systems

Abstract For many populations of estrogen‐sensitive neurons it remains unknown how they are associated with central nervous system circuitries that mediate estrogen‐induced modulation of behavioral components. With the use of double‐labeling immunohistochemistry and tracing techniques, the relationships of estrogen receptor (ER)‐α‐ and ER‐β‐immunoreactive (IR) neurons in the mouse brainstem and spinal cord to monoaminergic, cholinergic, and spinal projection systems are explored. Similar distributions of ER‐IR neurons were present in females and males, with differences in labeling intensity of ER‐α immunoreactivity among males and estrogen‐, and oil‐treated females. Barrington's nucleus, the ventrolateral medulla, and the nucleus of the solitary tract contained spinal‐projecting ER‐α‐IR neurons, whereas ER‐α‐IR neurons in the periaqueductal gray, parabrachial nucleus, and catecholaminergic A1 cell group received spinal input. Numerous tyrosine hydroxylase (TH)‐IR ER‐α‐IR neurons were present in the ventral periaqueductal gray, nucleus of the solitary tract, A1 cell group, and lumbosacral cord. The dorsal raphe nucleus contained ER‐α‐IR and ER‐β‐IR neurons that colocalized with serotonin (5HT), and the reticulotegmental nucleus contained 5HT‐IR ER‐α‐IR neurons. Fibers IR for vesicular acetylcholine transporter (VAChT), TH, and 5HT were located among ER‐α‐IR neurons in the dorsal horn and spinal autonomic regions. Robust staining for TH and VAChT, but not 5HT, was present among ER‐α‐IR neurons in the lumbosacral lateral collateral pathway. Possible modulatory actions of estrogen on each of these ER‐IR populations are discussed in the context of their specific function, including micturition, sexual behavior, ejaculation, cardiovascular and respiratory control, tactile and nociceptive sensory processing, anti‐nociception, endocrine regulation, and feeding. J. Comp. Neurol. 488:152–179, 2005. © 2005 Wiley‐Liss, Inc.