A neuroactive steroid 5alpha-androstane-3alpha,17beta-diol regulates androgen receptor level in astrocytes

Journal of Neurochemistry
Olga A AgapovaM Rosario Hernandez

Abstract

Optic nerve head (ONH) astrocytes from patients with glaucomatous optic neuropathy exhibit increased production of 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), a neuroactive metabolite of 5alpha-dihydrotestosterone (5alpha-DHT). To determine whether ONH astrocytes are androgen target cells, and whether 3alpha-diol is capable of regulating astrocyte functions, we studied the response of human ONH astrocytes to 3alpha-diol compared with 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one (R1881), a synthetic 5alpha-DHT agonist. In ONH astrocytes, both 3alpha-diol and R1881 increased protein levels of androgen receptor (AR) and glial fibrillary acidic protein (GFAP), however, only R1881 also increased the AR mRNA level and astrocyte proliferation. Both R1881 and 3alpha-diol rapidly activate the mitogen-activated protein kinase (MAPK) signaling pathway in ONH astrocytes, as confirmed by phosphorylation of extracellular signal-regulated kinase (ERK). 3Alpha-diol also activates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. 3Alpha-diol regulates the increase of AR protein level and the phosphorylation through the PI3K/Akt pathway, whereas R1881 regulates them through the MAPK/ERK pathway. Our findi...Continue Reading

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Citations

Jun 16, 2009·Journal of Glaucoma·Elaine C Johnson, John C Morrison
Jun 27, 2007·Investigative Ophthalmology & Visual Science·Elaine C JohnsonJohn C Morrison
May 12, 2009·BMC Medical Genomics·Tatiana NikolskayaValery I Shestopalov
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May 15, 2012·The Journal of Comparative Neurology·Ryan T JohnsonCynthia L Jordan
Jul 18, 2020·Journal of Cellular and Molecular Medicine·Zhan-Fei ZhangBi-Jun Huang

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