title: Deficiency of female sex hormones augments PGE2 and CGRP levels within midbrain periaqueductal gray.
abstract: The midbrain periaqueductal gray (PAG) is a substantial component of the descending modulatory network to control on nociceptive transmission and autonomic functions. Also, accumulated evidence has suggested that the PAG plays a crucial role in regulating migraine headache, a neurovascular disorder. The purpose of this study was to employ ELISA methods to examine the levels of prostaglandin E2 (PGE2) and calcitonin-gene related peptide (CGRP) in the PAG of rats who received ovariectomy and subsequent hormone replacement with 17β-estradiol, progesterone, or the combination of 17β-estradiol and progesterone. In addition, using Western blot analysis we examined expression of subtypes of PGE2 receptor in the PAG of rats with different conditions of female sex hormones. Results of our study demonstrated that lack of female sex hormones significantly increased the levels of PGE2 and CGRP in the dorsolateral PAG (P < 0.05) as well as expression of PGE2 EP3 receptors (P < 0.05). Furthermore, a liner relationship was observed between PGE2 and CGRP in the PAG (r = 092, P < 0.01). Also, inhibiting EP3 receptors by chronic administration of L-798106 (EP3 antagonist) into the lateral ventricles significantly attenuated expression of CGRP in the PAG of ovariectomized animals (P < 0.05 vs. vehicle control). Overall, our findings for the first time show that (1) circulating 17β-estradiol and/or progesterone influences the levels of PGE2 and CGRP in the PAG; (2) a lower level of 17β-estradiol and/or progesterone augments PGE2 and its EP3 receptor; and (3) PGE2 plays a role in regulating expression of CGRP in the PAG.
authors.affiliation: Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province 110001, China.
authors.forename: Jiuhan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Liaoning Provincial People's Hospital, Shenyang, Liaoning Province 110016, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hong Kong Claire Biological Technology, Hong Kong SAR of China, Hong Kong 999077, China.
authors.forename: Jingqing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Yu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR of China, Hong Kong 999077, China. Electronic address: gxinjin@gmail.com.
authors.forename: Xinjin
authors.initials: X
authors.lastname: Guo
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000172:deficiency*; D010052:Ovariectomy; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism
chemical_list: D004338:Drug Combinations; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011372:Progestins; D018078:Receptors, Prostaglandin E; D011374:Progesterone; D004958:Estradiol; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone
keywords: 17β-Estradiol; CGRP; EP(3); Midbrain PAG; PGE(2); Progesterone