Estrogen receptor‐α and neural circuits to the spinal cord during pregnancy

Abstract

Estrogen receptor immunoreactivity and mRNAs are present in spinal cord neurons in locations that are associated with sensory and autonomic innervation of female reproductive organs. The present study was undertaken to examine the expression of estrogen receptor-alpha in the spinal cord during different stages of pregnancy and to determine whether estrogen receptor-alpha-expressing neurons are related to uterine afferent nerves bringing information to the spinal cord at parturition. Immunohistochemistry showed estrogen receptor-alpha-immunoreactive neurons in the dorsal one-half of the spinal cord, i.e., dorsal horn, dorsal intermediate gray areas (dorsal commissural nucleus), and around the central canal and sacral parasympathetic autonomic nucleus of the lumbosacral spinal cord. Neurons in these areas corresponded topographically to the distribution of central processes of visceral primary afferent neurons (e.g., containing calcitonin gene-related peptide and substance P) that innervate and activate second-order spinal cord neurons (evidenced by their expression of Fos) at parturition. Western blots showed that estrogen receptor-alpha increases in the spinal cord, with a peak at day 20 of gestation, followed by a slight decrease by 2 days postpartum. These studies show that estrogen receptor-alpha is expressed by neurons in autonomic and sensory areas of the lumbosacral spinal cord that have connections with the female reproductive system and that the level of estrogen receptor-alpha changes over the course of pregnancy, which may follow profiles of steroid hormones. Many of these neurons may be involved in processing information related to reproductive organ function, changes during pregnancy, and relays to other CNS centers.

Carpal tunnel syndrome in postmenopausal women

“…Estrogen receptors are found throughout the central and peripheral nervous systems. In the peripheral nervous system, estrogen receptors are found in the spinal cord [12][13][14][15], dorsal root ganglia [16][17][18][19], autonomic pelvic ganglia [14,15], sympathetic ganglia [20,21], and Schwann cells [22]. Numerous studies have shown that estrogens affect the nervous system via both genomic and non-genomic mechanisms, including the development, proliferation, and regeneration of neuronal cells, gene expression, energy metabolism, hormone sensitivity, and the biosynthesis of structural proteins and enzymes [12,15,17,19,23].…”

Spinal Synthesis of Estrogen and Concomitant Signaling by Membrane Estrogen Receptors Regulate Spinal κ- and μ-Opioid Receptor Heterodimerization and Female-Specific Spinal Morphine Antinociception

“…Previous studies have shown that ER α and to a lesser extent ER β are present in neurons of the spinal cord dorsal horn (Papka et al, 2001; Gintzler et al, 2008) in areas that topographically correspond to the distribution of central processes of visceral primary afferent neurons (Papka et al, 2002; Vanderhorst et al, 2009). These areas also express opioid receptors, which localize to pre-synaptic terminals of primary sensory neurons as well as to their postsynaptic targets in laminae I and II (Kline and Wiley, 2008).…”

Long-term Estradiol-17.BETA. Administration Decreases the Number of Neurons in the Caudal Mesenteric Ganglion Innervating the Ovary in Sexually Mature Gilts

“…Also, significant reduction in the number of neurons displaying p75 protein has been observed at the end of pregnancy, when estrogen levels are increased [42]. Moreover, considering the expression of ERs by neurons in autonomic and sensory areas of the lumbosacral spinal cord that have connections with female reproductive system [43], it is possible that the reduction in the number of postganglionic neurons found in the present study may partly result from changes of the density of ERs receptors on preganglionic neurons in response to E2 treatment, which could ultimately affect both the morphology and activity of these cells and consequently disturb the neuronal network function.…”