Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 1/2011

01-05-2011 | Migraine Pathophysiology

Female reproductive steroids and neuronal excitability

Authors: C. Finocchi, M. Ferrari

Published in: Neurological Sciences | Special Issue 1/2011

Login to get access

Abstract

Oestrogen and progesterone have specific receptors in the central nervous system and are able to regulate neuronal development and plasticity, neuronal excitability, mitochondrial energy production, and neurotransmitter synthesis, release, and transport. On neuronal excitability, estradiol and progesterone seem to have an opposite effect, with estradiol being excitatory and progesterone and its derivative allopregnanolone being inhibitory. Estradiol augments N-methyl-d-aspartate-mediated glutamate receptor activity, while progesterone enhances gamma-aminobutyric acid-mediated chloride conductance. Sex steroid regulation of the balance of neuroexcitatory and neuroinhibitory activities may have a role in modulating clinical susceptibility to different neurological conditions such as migraine, catamenial epilepsy, premenstrual dysphoric disorder, and premenstrual syndrome.
Literature
1.
McEwen BS (2001) Invited review: estrogens effects on the brain: multiple sites and molecular mechanisms. J Appl Physiol 91:2785–2801PubMed
2.
3.
Guille C, Spencer S, Cavus I, Epperson CN (2008) The role of sex steroids in catamenial epilepsy and premenstrual dysphoric disorder: implications for diagnosis and treatment. Epilepsy Behav 13:12–24PubMedCrossRef
4.
Aguggia M, D’Andrea G, Bussone G (2007) Neurophysiology and neuromodulators. Neurol Sci 28(Suppl 2):S97–S100PubMedCrossRef
5.
Aurora SK, Barrodale P, Chronicle EP, Mulleners WM (2005) Cortical inhibition is reduced in chronic and episodic migraine and demonstrates a spectrum of illness. Headache 45:546–552PubMedCrossRef
6.
Moskowitz MA, Bolay H, Dalkara T (2004) Deciphering migraine mechanisms: clues from familial hemiplegic migraine genotypes. Ann Neurol 55:276–280PubMedCrossRef
7.
Rasmussen B, Jensen R, Schroll M, Olesen J (1991) Epidemiology of headache in a general population: a prevalence study. J Clin Epidemiol 44:1147–1157PubMedCrossRef
8.
Silberstein SD (2001) Hormone-related headache. Med Clin North Am 285:1017–1035CrossRef
9.
Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M (2001) Prevalence and burden of migraine in the United States: Results from the American Migraine Study II. Headache 41:646–657PubMedCrossRef
10.
Herzog AG (2008) Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure 17:151–159PubMedCrossRef
11.
Backstrom T, Andersson A, Andree L et al (2003) Pathogenesis of menstrual cycle-linked CNS disorders. Ann N Y Acad Sci 1007:42–53PubMedCrossRef
12.
Mensah-Nyagan AG, Do-Rego JL, Beaujean D, Luu-The V, Pelletier G, Vaudry H (1999) Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol Rev 51:63–81PubMed
13.
Woolley CS, McEwen BS (1993) Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 336:293–306PubMedCrossRef
14.
Gazzaley AH, Weiland NG, McEwen BS, Morrison JH (1996) Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus. J Neurosci 16:6830–6838PubMed
15.
Woolley CS, McEwen BS (1994) Estradiol regulates hippocampal dendritic spine density via an N-methyl-d-aspartate receptor-dependent mechanism. J Neurosci 14:7680–7687PubMed
16.
Rudick CN, Woolley CS (2001) Estrogen regulates functional inhibition of hippocampal CA1 pyramidal cells in the adult female rat. J Neurosci 21:6532–6543PubMed
17.
Wallis CJ, Luttge WG (1980) Influence of estrogen and progesterone on glutamic acid decarboxylase activity in discrete regions of rat brain. J Neurochem 34:609–613PubMedCrossRef
18.
Toran-Allerand CD, Guan X, MacLusky NJ et al (2002) ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. J Neurosci 22:8391–8401PubMed
19.
Smith SS (1989) Estrogen administration increases neuronal responses to excitatory amino acids as a long term effect. Brain Res 503:354–357PubMedCrossRef
20.
Wong M, Moss RL (1992) Long-term and short-term electrophysiological effects of estrogen on the synaptic properties of hippocampal CA1 neurons. J Neurosci 12:3217–3225PubMed
21.
Kokate TG, Svensson BE, Rogawski MA (1994) Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther 270:1223–1229PubMed
22.
Reddy DS, Castaneda DC, O’Malley BW, Rogawski MA (2004) Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice. J Pharmacol Exp Ther 310:230–239PubMedCrossRef
23.
Smith SS (2002) Withdrawal properties of a neuroactive steroid: implications for GABA(A) receptor gene regulation in the brain and anxiety behavior. Steroids 67:519–528PubMedCrossRef
24.
Gulinello M, Gong QH, Smith SS (2002) Progesterone withdrawal increases the alpha4 subunit of the GABA(A) receptor in male rats in association with anxiety and altered pharmacology: a comparison with female rats. Neuropharmacology 43:701–714PubMedCrossRef
25.
Smith SS, Gong QH, Hsu FC, Markowitz RS, French-Mullen JM, Li X (1998) GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 392:926–930PubMedCrossRef
26.
Smith SS, Ruderman Y, Frye C, Homanics G, Yuan M (2006) Steroid withdrawal in the mouse results in anxiogenic effects of 3alpha, 5beta-THP: a possible model of premenstrual dysphoric disorder. Psychopharmacology 186:323–333PubMedCrossRef
27.
Terasawa E, Timiras PS (1968) Electrical activity during the estrous cycle of the rat: cyclic changes in limbic structures. Endocrinology 83:207–216PubMedCrossRef
28.
Marcus EM, Watson CW, Goldman PL (1966) Effects of steroids on cerebral electrical activity. Epileptogenic effects of conjugated estrogens and related compounds in the cat and rabbit. Arch Neurol 15:521–532PubMed
29.
Landgren S, Backstrom T, Kalistratov G (1978) The effect of progesterone on the spontaneous interictal spike evoked by the application of penicillin to the cat’s cerebral cortex. J Neurol Sci 36:119–133PubMedCrossRef
30.
van den Maagdenberg AM, Pietrobon D, Pizzorusso T et al (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron 41:701–710PubMedCrossRef
31.
Eikermann-Haerter K, Kudo C, Moskowitz MA (2007) Cortical spreading depression and estrogen. Headache 47(Suppl 2):S79–S85PubMedCrossRef
32.
Sachs M, Pape HC, Speckmann EJ, Gorji A (2007) The effect of estrogen and progesterone on spreading depression in rat neocortical tissues. Neurobiol Dis 25:27–34PubMedCrossRef
33.
Smith MJ, Keel JC, Greenberg BD, Adams LF, Schmidt PJ, Rubinow DA, Wassermann EM (1999) Menstrual cycle effects on cortical excitability. Neurology 53:2069–2072PubMed
34.
Smith MJ, Adams LF, Schmidt PJ, Rubinow DR, Wassermann EM (2002) Effects of ovarian hormones on human cortical excitability. Ann Neurol 51:599–603PubMedCrossRef
35.
Inghilleri M, Conte A, Curra A, Frasca V, Lorenzano B, Berardellia A (2004) Ovarian hormones and cortical excitability. An rTMS study in humans. Clin Neurophysiol 115:1063–1068PubMedCrossRef
36.
De Tommaso M, Valeriani M, Sardaro M, Serpino C, Fruscolo OD, Vecchio E, Cerbo R, Livrea P (2009) Pain perception and laser evoked potentials during menstrual cycle in migraine. J Headache Pain 10(6):423–429PubMedCrossRef
37.
Herzog AG, Klein P, Ransil BJ (1997) Three patterns of catamenial epilepsy. Epilepsia 38:1082–1088PubMedCrossRef
38.
Herzog AG (2008) Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure 17:151–159PubMedCrossRef
39.
Sundstrom I, Backstrom T (1998) Citalopram increases pregnanolone sensitivity in patients with premenstrual syndrome: an open trial. Psychoneuroendocrinology 23:73–88PubMedCrossRef
40.
Epperson CN, Haga K, Mason GF et al (2002) Cortical gammaaminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry 59:851–858PubMedCrossRef
41.
Somerville BW (1972) The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 22:355–365PubMed
Metadata
Title
Female reproductive steroids and neuronal excitability
Authors
C. Finocchi
M. Ferrari
Publication date
01-05-2011
Publisher
Springer Milan
Published in
Neurological Sciences / Issue Special Issue 1/2011
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-011-0532-5

Other articles of this Special Issue 1/2011

Neurological Sciences 1/2011 Go to the issue

Treatment

Migraine with aura: conventional and non-conventional treatments

ANIRCEF - HCNE Joint Meeting

What future for treatment of chronic migraine with medication overuse?

Migraine and Depression

Migraine and depression: common pathogenetic and therapeutic ground?

ANIRCEF - HCNE Joint Meeting

Neuromodulation in drug-resistant primary headaches: what have we learned?

Brief Communication

Possible relationships between headache–allodynia and nocturnal sleep breathing

Brief Communication

A longitudinal evaluation of changes in disability and quality of life in a sample of women with migraine