Steroids-dopamine interactions in the pathophysiology and treatment of CNS disorders.
BACKGROUND
Dopamine cell loss is well documented in Parkinson's disease and dopamine hypofunction is proposed in certain depressive states. At the opposite, dopamine hyperactivity is an enduring theory in schizophrenia with extensive supporting evidence.


OBJECTIVE
This article reviews the sex differences in these diseases that are the object of many studies and meta-analyses and could be explained by genetic differences but also an effect of steroids in the brain. This article then focuses on the extensive literature reporting on the effect of estrogens in these diseases and effects of the other ovarian hormone progesterone as well as androgens that are less documented. Moreover, dehydroepiandrosterone, the precursor of estrogens and androgens, shows effects on brain dopamine neurotransmission that are reviewed. To investigate the mechanisms implicated in the human findings, animal studies are reviewed showing effects of estrogens, progesterone, and androgens on various markers of dopamine neurotransmission under intact as well as lesioned conditions.


CONCLUSIONS
For possible future avenues for hormonal treatments in these central nervous system diseases, we discuss the effects of selective estrogen receptor modulators (SERMs), the various estrogen receptors and their specific drugs as well as progesterone drugs.


CONCLUSIONS
Clinical and experimental evidence supports a role of steroid-dopamine interactions in the pathophysiology of schizophrenia, depression and Parkinson's disease. Specific steroidal receptor agonists and SERMs are available for endocrine and cancer treatments and could find other applications as adjunct treatments in central nervous system diseases.
Sánchez
Maria Gabriela
MG
Centre Hospitalier Universitaire de Québec, CHUL Pavillon, Canada.
Bourque
Mélanie
M
Morissette
Marc
M
Di Paolo
Thérèse
T
D000375:Aging; D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D011987:Receptors, Steroid / Q000502:physiology; D012727:Sex Characteristics; D013256:Steroids / Q000378:metabolism* / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D011987:Receptors, Steroid; D013256:Steroids; D004298:Dopamine