Accutane Inhibits Transcription of 5-alpha Reductase Type-I

Lasting side effects from pharmaceuticals Forums Group Forums Accutane Biological Effects of Isotretinoin/Accutane Accutane Inhibits Transcription of 5-alpha Reductase Type-I

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  • #1979
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    dubya_b
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    An assay of gene expression changes in the skin cells of patients exposed to Isotretinoin offers compelling confirmation of 5-alpha reductase inhibition during treatment.

     

    A. M. Nelson, W. Zhao, K. L. Gilliland, A. L. Zaenglein, W. Liu, and D. M. Thiboutot, “Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action,”Dermato-Endocrinology, vol. 1, no. 3, pp. 177–187, May 2009.

     

    Full PDF link:

     

    Levels of cDNA obtained from RT-qPCR indicated a nearly 3-fold decrease in the expression of SRD5A1, the gene encoding 5-alpha reductase type-I, after 8 weeks of Isotretinoin therapy.

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  • #2013
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    pete
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    That’s a useful piece of research. There is even a table detailing the affected genes, their titles, and levels of change.

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  • #2027
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    dubya_b
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    Thanks. Another interesting bit is the column on the far right of that table denotes the presence of RAR and RXR response elements in the regulatory regions in many of the genes being studied. Nice that the authors presented that in the info.

    Besides 5-a reductase type-I, it is also worth pointing out the 6-fold decrease in HSD3B1 (encodes the 3b-HSD type-I enzyme) during Accutane treatment. This enzyme is responsible for conversion of pregnenolone and DHEA into all other steroid hormones. These include androgens, estrogens, progestins, and gluccocorticoids (“cortisols”). It is a critical step in the pathway of steroid hormone biosynthesis.

    https://en.wikipedia.org/wiki/3%CE%B2-Hydroxysteroid_dehydrogenase

    There is a second gene encoding a second isoform of the enzyme that is not included on the table in the study. Not sure if it was ignored, or not found to be influenced by isotretinoin. Type-II mRNA is more highly expressed in steroidogenic tissues and the type-I is mRNA more pronounced in peripheral tissues, including skin, retina,  and prostate.

    mRNA expression and estimated protein expression levels can be found on these pages:

    http://www.genecards.org/cgi-bin/carddisp.pl?gene=HSD3B1

    http://www.genecards.org/cgi-bin/carddisp.pl?gene=HSD3B2

     

    There was also a 4-fold decrease in HIST1H1C mRNA. This encodes histone H1.2, which is a DNA scaffolding protein thought to link DNA-wrapped nucleosomes together. But its role in regulating gene expression is unclear at the moment.

     

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  • #2044
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    pete
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    Wow, that is deep. The article should hopefully get picked up by researchers in this area – I think it would be of real use in understanding these medications.

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