Diversity of mechanisms involved in aromatase regulation and estrogen action in the brain.
BACKGROUND
The mechanisms through which estrogens modulate neuronal physiology, brain morphology, and behavior in recent years have proven to be far more complex than previously thought. For example, a second nuclear estrogen receptor has been identified, a new family of coregulatory proteins regulating steroid-dependent gene transcriptions was discovered and, finally, it has become clear that estrogens have surprisingly rapid effects based on their actions on cell membranes, which in turn result in the modulation of intracellular signaling cascades.


METHODS
This paper presents a selective review of new findings in this area related to work in our laboratories, focusing on the role of estrogens in the activation of male sexual behavior. Two separate topics are considered. We first discuss functions of the steroid receptor coactivator-1 (SRC-1) that has emerged as a key limiting factor for behavioral effects of estradiol. Knocking-down its expression by antisense oligonucleotides drastically inhibits male-typical sexual behaviors. Secondly, we describe rapid regulations of brain estradiol production by calcium-dependent phosphorylations of the aromatase enzyme, themselves under the control of neurotransmitter activity.


CONCLUSIONS
These rapid changes in estrogen bioavailability have clear behavioral consequences. Increases or decreases in estradiol concentrations respectively obtained by an acute injection of estradiol itself or of an aromatase inhibitor lead within 15-30 min to parallel changes in sexual behavior frequencies.


CONCLUSIONS
These new controls of estrogen action offer a vast array of possibilities for discrete local controls of estrogen action. They also represent a formidable challenge for neuroendocrinologists trying to obtain an integrated view of brain function in relation to behavior.
Charlier
Thierry D
TD
GIGA Neurosciences, University of Liège, 4000 Liège, Belgium.
Cornil
Charlotte A
CA
Ball
Gregory F
GF
Balthazart
Jacques
J
D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D004958:Estradiol / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000378:metabolism; D012725:Sexual Behavior / Q000187:drug effects / Q000502:physiology*; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D047072:Aromatase Inhibitors; D004967:Estrogens; D018377:Neurotransmitter Agents; D011960:Receptors, Estrogen; D004958:Estradiol; D001141:Aromatase; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D002118:Calcium