
Originally Posted by
Pinnacle
Zero facts?
Attack?
If it's easy to post studies,then why haven't you to suport you claim?
Here's mine...show me yours.....
Specific papers often cited to support downregulation of the AR
Endocrinology (1981) 104 4 1431. This paper compares the normal state of the rat to the castrated state, and the muscle cytosol AR concentrations of the female rat to the intact (sham-operated) male rat.
Objections to this study include the fact that the effect of supraphysiological levels of androgen was not studied; that cytosolic measurements of AR are unreliable since varying percentages of ARs may concentrate in the nuclear region, and these are more indicative of activity; and that castration of rats is notorious for producing false conclusions. The cells, and indeed the entire system of the animal, undergo qualitative change (e.g., cessation of growth) from the castration relative to the sham-operated animals. Testosterone levels are not the only thing which change upon castration. Another objection is that estrogen was not controlled and the effects of estrogen were not determined or accounted for. Estrogen levels certainly were not constant in this experiment.
Molecular Endocrinology (1990) 4 22. AR mRNA level, in vitro, was seen to increase as androgen levels were reduced below normal. Supraphysiological levels were not tested. Northern blot analysis was used. AR levels were not measured.
Molecular and Cellular Endocrinology (1991) 76 79. In human prostate carcinoma cells, in vitro, androgen resulted in downregulation of AR mRNA relative to zero androgen levels. Levels of androgen receptor, however, increased, relative to when androgen level was zero, by a factor of two. The researchers noted, "At 49 hours, androgen receptor protein increased 30% as assayed by immunoblots and 79% as assayed by ligand binding" [the later method is the more reliable and indicative of biological effect.]
Molecular Endocrinology (1993) 7 924. In vitro, it was determined by Northern blot analysis that mRNA levels decreased when supraphysiological levels of androgen were compared to zero androgen in cancer cells. Levels of ARs were measured, and there was no observed decrease despite the observed decrease in mRNA level (as measured by Northern blot.)
Molecular and Cellular Endocrinology (1995) 115 177. COS 1 cells were transfected with human AR DNA with the CMV promoter. The authors state that the DNA sequence responsible for downregulation of the AR is encoded within the AR DNA, not the promoter region. Dexamethasone [a glucocorticoid drug similar to cortisol] was observed to result in downregulation of AR mRNA relative to zero dexamethasone level. Androgen also had this effect, but did not result in lower levels of androgen receptors. This was attributed to increase in androgen receptor half life caused by androgen administration. The observed androgen downregulation effect relative to zero androgen ended at a concentration of 0.1 nanomolar of androgen (methyltrienolone) – higher doses, to 100 nanomolar, resulted in no further downregulation of AR mRNA production.