API

Relationship: 1496

Title

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7α-hydroxypregnenolone synthesis in the brain, decreased leads to Dopamine release in the brain, decreased

Upstream event

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7α-hydroxypregnenolone synthesis in the brain, decreased

Downstream event

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Dopamine release in the brain, decreased

Key Event Relationship Overview

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AOPs Referencing Relationship

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Cynops pyrrhogaster Cynops pyrrhogaster NCBI

Sex Applicability

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Sex Evidence
Male Moderate

Life Stage Applicability

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Term Evidence
Adult, reproductively mature

Key Event Relationship Description

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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

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Biological Plausibility

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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.

 

Empirical Evidence

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  • 7α-hydroxypregnenolone concentration in the brain of salmon prior to upstream migration was decreased using aminoglutethimide (AG) injection (CYP11A inhibitor) and lead to a decreased dopamine concentration in the telencephalon compared to control. This effect was rescued with intracerebroventricular injection of 7α-hydroxypregnenolone. Simultaneous measurements of hypothalamic dopamine concentration showed an absence of variation after AG-injection or AG+7 PREG (Haraguchi et al., 2015)
  • Tyrosine hydroxylase (TH) is a marker of dopamine neurons. Immunolabelling of CYP7B and TH revealed that these enzymes are  expressed in two different cell populations in the salmon magnocellular preoptic nucleus and that they are in close proximity to each other (Haraguchi et al., 2015).
  • 7α-hydroxypregnenolone (1 ng) was injected in non-breeding male newt and several monoamines concentration were measured using HPLC-electrochemical detection. 7α-hydroxypregnenolone increased dopamine concentration in the rostral brain region including striatum. No change was observed in the concentration of any other monoamine (Matsunaga et al., 2004).
  • Newt brain incubated in vitro with 7α-hydroxypregnenolone (0, 10−8, 10−7, or 10−6 M) induced a dose-dependent increase of dopamine concentration after 10 minutes (Matsunaga et al., 2004).

Uncertainties and Inconsistencies

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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.

Quantitative Understanding of the Linkage

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One study specifically performed a dose-reponse experiment for 7α-hydroxypregnenolone in relation to dopamine concentration.

  • Newt brain incubated with 7α-hydroxypregnenolone (0, 10−8, 10−7, or 10−6 M) induced a dose-dependent increase of dopamine concentration after 10 minutes (Matsunaga et al., 2004). 

Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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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.