Finasteride blocks progesterone:allopregnanolone conversion

#1

Neurosteroids, and the Hormonal Basis of Catamenial (Menstrual) Epilepsy

FULL TEXT (PDF): labs.ninds.nih.gov/rogawski/pdfs … ol2003.pdf


Although this study refers to women, it also confirms that Finasteride blocks the conversion of Progesterone to Allopregnanolone (a neurosteroid with anticonvulsant properties) and its effect on GABA.

Furthermore, there is a nice diagram ILLUSTRATING how this conversion is blocked.

Also mentioned in the diagram is that “In humans, finasteride is a more potent inhibitor of the type II isoenzyme (predominantly expressed in the male urogenital tract) than the type I isoenzyme (liver, skin, and brain)…”


SELECTED ABSTRACT:

In the mid-1980s it was found that a progesterone metabolite allopregnanolone, often referred to as a “neurosteroid,” is a powerful positive allosteric modulator of GABAA receptors8 (Fig).

As with other agents that act to enhance GABAergic inhibition, allopregnanolone has anticonvulsant properties.9 Thus, it seemed possible that the anticonvulsant activity of progesterone could be because of its conversion to allopregnanolone.

This conjecture was proved in animals using finasteride, a 5a-reductase inhibitor, to block the first step in the conversion of progesterone to allopregnanolone10 and more recently confirmed in female
mice with an induced null mutation in a 5a-reductase gene.11

Moreover, in an animal model of perimenstrual catamenial epilepsy, it was demonstrated that withdrawal of allopregnanolone (like that which occurs at menstruation in concert with decreasing levels of progesterone) is associated with a marked increase in seizure susceptibility.12,13

This is in part undoubtedly because of the loss of the anticonvulsant effects of allopregnanolone, but there also may be changes in the properties of GABAA receptors that predispose to heightened seizure susceptibility.14,15

…A brief report in this issue of the Annals by Herzog and colleagues19 provides anecdotal evidence supporting the concept that progesterone’s therapeutic activity in catamenial epilepsy requires conversion to a 5a-reduced metabolite.


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#2

I think the link to this doesnt work. I also find it difficult to locate some other research links. Has someone downloaded all or most of them to send me the missing ones?? We need all such documents. Some research can be very crucial to

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