31-08-2016, 09:27 PM
From the study:
Mechanisms of oestrogen elimination
The behavioural inhibition resulting from the pharmacological blockade of aromatase suggests that there must exist some mechanism(s) able to rapidly clear locally-produced oestrogens to terminate their effects. The elimination of plasma oestrogen is ensured through excretion following their conversion into inactive (or less active) water-soluble metabolites by oxidative metabolism and conjugation (89).
This metabolism mainly occurs in the liver but detectable levels of catabolic activity are also observed in the brain (90–92). Interestingly, in addition to its oestrogen synthase activity, purified aromatase from human placental microsomes also catalyses oestrogen 2-hydroxylation.
It is thus possible that the same enzymatic protein is involved in both the production and the conversion of oestrogens (for further information, see (64)). Finally, passive dilution could also contribute to the rapid equilibration of the high locally synthesized oestrogen concentrations with the much lower brain concentrations.
At such concentrations, brain-derived oestrogens would then no longer be able to sustain membrane effects resulting in their termination. The half-life of oestradiol in the brain is not known, but calculations derived from pharmacokinetic data estimated that its half-life in the blood ranges from 5 to 15 min (63). Therefore, it is conceivable that oestrogen dilution combined with its enzymatic degradation could interrupt oestrogen- dependent signalling in the brain within minutes.
Mechanisms of oestrogen elimination
The behavioural inhibition resulting from the pharmacological blockade of aromatase suggests that there must exist some mechanism(s) able to rapidly clear locally-produced oestrogens to terminate their effects. The elimination of plasma oestrogen is ensured through excretion following their conversion into inactive (or less active) water-soluble metabolites by oxidative metabolism and conjugation (89).
This metabolism mainly occurs in the liver but detectable levels of catabolic activity are also observed in the brain (90–92). Interestingly, in addition to its oestrogen synthase activity, purified aromatase from human placental microsomes also catalyses oestrogen 2-hydroxylation.
It is thus possible that the same enzymatic protein is involved in both the production and the conversion of oestrogens (for further information, see (64)). Finally, passive dilution could also contribute to the rapid equilibration of the high locally synthesized oestrogen concentrations with the much lower brain concentrations.
At such concentrations, brain-derived oestrogens would then no longer be able to sustain membrane effects resulting in their termination. The half-life of oestradiol in the brain is not known, but calculations derived from pharmacokinetic data estimated that its half-life in the blood ranges from 5 to 15 min (63). Therefore, it is conceivable that oestrogen dilution combined with its enzymatic degradation could interrupt oestrogen- dependent signalling in the brain within minutes.