Estrogen receptor-alpha and neural circuits to the spinal cord during pregnancy

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.