If women had no prolactin receptors on cells in their mammary glands, they would not produce milk when they were nursing. Prolactin receptors are also found in other organs including the lung and the colon. The only problem is that these receptors are sort of like cellular wiring, and when the...
www.sciencedaily.com
HDAC4/9 are present in healthy hair follicles and
this study reveals they are strongly associated with Androgenetic Alopecia. It was always assumed that this association was due to them being corepressors of the AR, but they are also corepressors of the PRLR.
I think the balance of HDACs and HATs is skewed in Androgenetic Alopecia creating upregulation of AR and PRLR, which ultimately represses canonical Wnt signaling, causing a progressively shorter anagen phase. From the top SNPs in this study there is the AR of course, then genes that regulate AR and PRLR transactivation, PAX1 and TWIST which are involved in Wnt signaling and upregulated by PRLR. It certainly seems like Androgenetic Alopecia is driven by coactivation of the AR and PRLR. AR activation itself recruits histone acetyltransferases, which upregulate PRLR. Crosstalk between the two then takes place.
ASC-J9 may be an ideal AR antagonist to use with HMI-115, as curcumin inhibits HATs.
HAT inhibitors have shown success in prostate cancer.
"A limited number of HAT inhibitors are in preclinical or clinical trials, with p300/CBP and P/CAF-specific inhibitors showing the most promising effects"
The androgen receptor (AR) is a ligand activated transcription factor and member of the steroid hormone receptor (SHR) subfamily of nuclear receptors. In the early stages of prostate carcinogenesis, tumour growth is dependent on androgens, and AR directly ...
www.ncbi.nlm.nih.gov
Estradiol promotes prolactin transactivation by inducing histone acetylation through ERα, but the predominant estrogen receptor in the scalp is ERβ and it silences ERα. So estradiol does not upregulate prolactin signaling in the hair follicle, despite upregulating it in other tissues.
Abstract. Transcription of the prolactin gene is dynamically controlled by positive and negative hormone signals that target the regulatory promoter region. Bas
academic.oup.com
HDAC inhibitors also work for prostate cancer, through inhibiting HSP90.
The androgen receptor (AR) is a ligand activated transcription factor and member of the steroid hormone receptor (SHR) subfamily of nuclear receptors. In the early stages of prostate carcinogenesis, tumour growth is dependent on androgens, and AR directly ...
www.ncbi.nlm.nih.gov
Prolactin actually upregulates HSP90
Request PDF | ATM Is Required for the Prolactin-Induced HSP90-Mediated Increase in Cellular Viability and Clonogenic Growth After DNA Damage | Prolactin acts as a survival factor for breast cancer cells, but the prolactin signaling pathway and the mechanism is unknown. Previously, we... | Find...
www.researchgate.net
It is theorized that in castration resistant prostate cancer AR activation is continued in part by "mechanisms including activation of kinase pathways that can both stabilize AR and enhance its transcriptional activity and upregulations of AR coactivators that increase AR mediated transcription. These sensitize AR to lower levels of ligand."
When prostate cancers progress following androgen depletion therapy, there are currently few treatment options with only one, docetaxel, that has been shown to prolong life. Recent work has shown that castration resistant prostate cancers (CRPC) continue ...
www.ncbi.nlm.nih.gov
Prolactin upregulates all of these pathways that hypersensitize the AR.
Also of importance, HSP90 promotes transcription of Twist1. Twist1 ablation results in perpetual anagen phase in mice.
Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT...
pubmed.ncbi.nlm.nih.gov
You can see from all this that the AR and PRLR are very interconnected. It's not hard to imagine that silencing the PRLR would stop the positive feedback loop between the two receptors and reverse male pattern baldness in a more potent and lasting way than current treatments, which is what was observed in stump-tailed macaques. Returning AR sensitivity to normal and restoring homeostasis could give lasting results that simple DHT inhibition does not.
Ultimate hair loss stack?: HMI-115, ASC-J9, Estriol. Nothing else needed for full reversal?
