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7α-hydroxypregnenolone synthesis in the brain, decreased leads to Dopamine release in the brain, decreased
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Inhibition of CYP7B activity leads to decreased reproductive success via decreased locomotor activity||adjacent||Low||Low||Florence Pagé-Larivière (send email)||Not under active development|
|Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior||adjacent||Florence Pagé-Larivière (send email)||Not under active development|
|Cynops pyrrhogaster||Cynops pyrrhogaster||NCBI|
Life Stage Applicability
|Adult, reproductively mature|
Key Event Relationship Description
7α-hydroxypregnenolone is synthesized in the diencephalon and the rhombencephalon (newt only) and has a paracrine effect on dopaminergic neurons that project into the telencephalon including the striatum.
Evidence Supporting this KER
7α-hydroxypregnenolone cannot be directly related to dopamine release since it has no known receptor and the cells that synthesize it are not in direct contact with the dopaminergic neurons. However, it was shown that 7α-hydroxypregnenolone release induces dopamine secretion in the brain.
Uncertainties and Inconsistencies
Since the neurosteroid receptor has yet to be identified, no direct interaction between 7α-hydroxypregnenolone and dopaminergic neuron has been demonstrated. It is thus possible that an intermediate event takes place in between to indirectly connect the neurosteroid to dopamine release.
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Haraguchi, S., Yamamoto, Y., Suzuki, Y., Hyung Chang, J., Koyama, T., Sato, M., Mita, M., Ueda, H., and Tsutsui, K. (2015). 7alpha-Hydroxypregnenolone, a key neuronal modulator of locomotion, stimulates upstream migration by means of the dopaminergic system in salmon. Sci Rep 5, 12546.
Matsunaga, M., Ukena, K., Baulieu, E.E., and Tsutsui, K. (2004). 7alpha-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system. Proc Natl Acad Sci U S A 101, 17282-17287.