Some new information from a just concluded study may clarify how DHT affects hair loss and how Propecia (Finasteride) helps to stop hair loss and regrow hair.
Dr. Marty Sawaya and Dr. Maria Hordinsky recently completed a study on the effects of finasteride that showed some interesting results. They discussed their results during a lecture at the World Hair Society meeting last week in Orlando, Florida.
“Some of the work we’ve recently done in a Merck education grant was to look at cell death factors in apoptosis, but we also looked at the A and B forms of the androgen receptor and found that this is switching with finasteride treatment,” said Dr. Sawaya.
Androgens are male hormones and androgen receptors are the cell structures that the hormones bind to in the cells to cause different hormonal effects in the body, such as the stimulation or inhibition of hair growth. Recent studies (see study below) have shown that there is more than one type of androgen receptor, an A form and a B form. Different receptor forms can have different activities when binding with the same hormone, so it is possible that the A form of the androgen receptor causes hair growth inhibition when it predominates in a follicle, while the B form promotes normal growth.
“Two forms of the receptor exist…” reported Dr. Sawaya, “The B form is thought to predominate and about 80% is expressed in normal cells while the A form is about 20% of the expressed form of the androgen receptor. We find that in male pattern hair loss, those men affected with hair loss, there’s more of a switch to the A form rather than the B form which should be there. So maybe the A form is signalling some sort ‘alopecia’ aspect verses the B form being the good one.”
Hairs in the back of the scalp have a normal ratio of A and B androgen receptors, while Dr. Sawaya’s report shows that hairs on the top of the scalp in balding men have more A receptors than B receptors. Dr. Sawaya’s recent study showed that with the use of Finasteride, androgen receptors are switching back to the B form. This may further expand our knowledge of how DHT causes hair loss and how Finasteride prevents further loss and regrows hair.
In further news on Propecia, Dr. Sawaya and Dr. Hordinsky also stated that Merck is expected to release the final results of the 5 year study on Propecia at next weeks American Academy of Dermatology (AAD) meeting. Regrowth.com will be covering the AAD meeting and will be reporting any results presented.
Functional activities of the A and B forms of the human androgen receptor in response to androgen receptor agonists and antagonists.
Mol Endocrinol 1998 May;12(5):654-63 (ISSN: 0888-8809)
Gao T; McPhaul MJ
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
The androgen receptor (AR) is present in many cells in two forms. The B form migrates with an apparent mass of 110 kDa and constitutes more than 80% of the immunoreactive receptor in most cell types. The A form of the AR migrates with an apparent mass of 87 kDa, appears to derive from internal translation initiation at methionine-188 in the AR open-reading frame, and usually constitutes 20% or less of the immunoreactive AR present. Previous experiments designed to examine the functional capacity of the A and B forms of the AR have been hampered by marked differences in the expression levels of the two isoforms, as the nucleotide sequence surrounding the codon encoding methionine-188 causes it to be used inefficiently as a translation initiation site. To circumvent this, we altered the nucleotide sequence surrounding methionine-188 to render it more similar to that surrounding the codon encoding methionine-1. Transfection of a cDNA containing these changes resulted in similar levels of expression of A and B forms of the AR as assessed by immunoblot assays using antibodies directed at an epitope preserved in both. Functional activities of these cDNAs were assessed using cotransfection assays that employed two model androgen-responsive genes (MMTV-luciferase and PRE2-tk-luciferase) in response to mibolerone, a potent androgen agonist, in three different cell lines. These studies demonstrated subtle differences in the activities of the A and B isoforms, which depended on the promoter and cell context. Additional studies failed to reveal any major differences in the responses of the AR-A and AR-B isoforms to a variety of androgen agonists and antagonists, suggesting that the previously reported functional defect of the AR-A is due principally to its level of expression. When assays of AR function are performed under conditions in which levels of expression of the two isoforms are equivalent, the AR-A and AR-B possess similar functional activities.