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Progesterone metabolites are present on the membrane of ER/PR + as well as ER/PR - breast cancer cell lines.  The balance of 5 alpha pregnane:3 alpha pregnane regulates tumor genesis.  Estradiol increased 5 alpha pregnane receptors as well as 5 alpha pregnane unregulated itself via autocrine activity.  The 3 alpha pregnenes, 3 alpha hydroxyprogesterone and 20 alpha-dihydroprogesterone, decrease the 5 alpha pregnane receptors via paracrine activity.

Estrogen receptors alpha and beta show dominance in the proliferative phases, with alpha isoform predominating.  In the secretory phase, less expression of ER was present. ER alpha was predominantly expressed in the epithelial and stromal cells in the proliferative phase.  ER beta was predominantly expressed in glandular cells in the same proliferative phase.   in the luteal phase, ER alpha expression declined in the funtionalis layers.  ER alpha in the basalis remained unchanged.  ER beta in the functionalis layers also declined in the luteal phase.   No relative change was found in the weak expression of ER alpha/beta in the myometrium.

New understanding in progesterone metabolites.  These are not waste products, but are indeed active. This in vitro study found the balance of 5 alpha pregnenes and 3 alpha pregnenes, particularly 3 alpha HP promotes carcinogenesis or inhibits.  These receptors were found in all 4 breast cell lines evaluated.  

The receptors for 5 alpha progesterone and 3 alpha hydroxyprogesterone are distinct from other hormone receptors.  These receptors are plasma membrane bound.  Through these receptors, these progesterone metabolites initiate autocrine and paracrine activity.  E2 increased 5 alpha progesterone receptors.  This is very important in ER-/PR- breast cancer, but does still have significance in ER+/PR+ cancer as well.

Progesterone metabolites play key role in breast cancer carcinogenesis or inhibition of carcinogenesis.  The key active progesterone metabolites discussed in this article are 5 alpha pregnene and 3 alpha hydroxyprogesterone.

5 alpha androstanediol promotes prostate cancer growth and survival independent of androgen receptors.   This study didn't clarify the mechanism.  We no know that this occurs via estrogen receptor alpha.  Thus a Testosterone metabolite signals through an estrogen receptor.

Great article!!  Nice discussion of the complexity of hormones.  Women on aromatase inhibitors can make estrogen from Testosterone.  This is important with estrogen sensitive cancer as in breast cancer.  This will occur via alternative pathways: Testosterone to DHT via 5 alpha reductase and then DHT to 3 beta androstanediol via 3 beta HSD.  3 beta androstanediol is a male hormone metabolite that binds to estrogen receptors.  The affinity is less than Estradiol, but appears to have a higher affinity for ER beta over ER alpha. 

This study proposes that testosterone therapy aids in renal dysfunction in men.  However, they document that IL-6 and TNF-alpha and oxidative stress are a part of this process. What they fail to mention is that aromatase activity and conversion of T to E in men increases IL-6 and TNF-alpha.  Studies have also shown that T decreases TNF-alpha. Very likely, it is high aromatase activity causing the effects documented by this study.

good review of 5-alpha reductase inhibitor and prostate pathophysiology.  Type I is increased in prostate cancer.  

interesting read on hormones and tourette's.. Proposed that 5 alpha reductase activity is involved in worsening of tics.  This makes sense as Testosterone in men with low T is known to increase dopamine and dopaminergic dysfunction is known to play a role in tourette's;  the clinical presentation of girls vs boys is very different.  The authors of this article propose that 5 alpha reductase activity controls a back door method where by progesterone is converted to androgens.

Great read on the regulation of the androgen receptor by the different iso forms of 5-alpha reductase and HSD.

This article discusses the failure of androgen deprivation therapy and prostate cancer.  This failure is quite common.  The authors point to alpha-DHT as the primary mechanism through AR stimulation.  However, we know that DHT metabolites also stimulate estrogen receptors.

mechanism of peripheral inflammation , via IFN-alpha and IL-6, contribution to depression

finasteride lacks the 5 alpha reductase specificity (type 1 > 2) for high grade prostate cancer.

Zinc deficiency associated with low 5-alpha reductase activity and increased aromatase activity.  Additionally, low zinc was associated with decreased LH and testosterone levels in male rats.

Very nice study.  The authors looked at normal prostate, early disease and late stage prostate cancer.  The authors found that ER beta expression, as a general rule, was lost as progression occurred to the high-grade dysplasias and grad 4/5 carcinomas of the prostate.  Early low/moderate dysplasia was associated with an increase in ER beta--the authors propose that this was due to an attempt of the basal epithelium to counter the paracrine effect of ER alpha.   In contrast, androgen receptors appeared to be equally expressed across all.

5 alpha reductase inhibitor therapy reduces PSA and prostate volume.  The level of change may be used to aid in prostate cancer diagnosis.  Those with eventual diagnosis had Gleason 7 or higher.

GLA found to inhibit 5 alpha reductase activity in prostate cancer cells.

5 alpha reductase inhibitor, finasteride inhibits pro-tumor progesterone metabolite pathway.