finasteride, Propecia
Androgen responsive genes as they affect hair growth.

Sawaya ME, Keane RW, Blume-Peytavi U, Mullins DL, Nusbaum BP, Whiting D, Nicholson DW.

ARATEC Research PO Box 7, Ocala, FL 34478, USA. Aratec worldnet.att.net

Finasteride has been shown to be an effective treatment for men with androgenetic alopecia (AGA) as it restores hair growth to miniaturized hair follicles on the top of the scalp [1]. Caspases are regulators of programmed cell death, and very likely some specific caspases may function as mediators of the hair growth cycle. It is unclear whether finasteride influences the regulation of apoptosis via caspases in the hair follicle. Very little information is available regarding the role of caspases present in human hair follicles in normal scalp and in androgenetic alopecia. In this study we have analyzed the family of caspases, 1-10 along with usurpin, and XIAP, in men with normal scalp and in men with androgenetic alopecia before and after 6 months treatment with 1 mg oral finasteride treatment. Caspases 1, 3, 8 and 9 were detected predominantly within the isthmic and infundibular hair follicle area for both normal and AGA patients, however the expression of all factors, especially caspase 3 was greater in the AGA group than in the normal scalp group. AGA men had the same caspase factors but with greater expression. In the same AGA men treated with finasteride for 6 months, the expression of these factors was similar to levels in the normal group. Results from our study indicate caspase 3 to be of primary importance in normal hair homeostasis and that DHT may be signaling greater expression of caspases, inducing apoptosis in androgenetic alopecia. In conclusion, DHT may selectively regulate the caspase genes which play an important role in signaling programmed cell death, affecting the hair growth cycle.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11399535&dopt=Abstract finasteride Propecia



finasteride, Propecia
Finasteride therapy does not alter bone turnover in men with benign prostatic hyperplasia--a Clinical Research Center study.

Tollin SR, Rosen HN, Zurowski K, Saltzman B, Zeind AJ, Berg S, Greenspan SL.

Charles A. Dana Research Institute, Boston, Massachusetts, USA.

Benign prostatic hyperplasia is often treated with finasteride, which inhibits the conversion of testosterone to dihydrotestosterone (DHT). Aside from the prostate, other androgen-dependent tissues seem to be unaffected by selective DHT deficiency, but the effect on bone density in humans has not yet been defined. To study this question, we compared indices of bone turnover and bone mineral density in 35 men treated with finasteride with controls. Bone resorption was assessed by measuring urinary excretion of N-telopeptide cross-links of type I collagen and hydroxyproline, and bone formation was assessed by measuring serum osteoncalcin and bone-specific alkaline phosphatase. Bone density of the spine and hip were assessed by dual energy x-ray absorptiometry. We found that finasteride-treated patients had mean DHT levels 81% lower than controls (P < 0.0001). There were no significant differences between the two groups in any of the markers of bone turnover or measures of bone density. These results suggest that testosterone can maintain bone density in men even in the absence of DHT. Although long term studies are needed, our results suggest that men who take finasteride are not at increased risk for bone loss.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8772571&dopt=Abstract finasteride Propecia



finasteride, Propecia
Synthesis of 5,6,6-[2H3]finasteride and quantitative determination of finasteride in human plasma at picogram level by an isotope-dilution mass spectrometric method.

Guarna A, Danza G, Bartolucci G, Marrucci A, Dini S, Serio M.

Dipartimento di Chimica Organica Ugo Schiff, Universita di Firenze, Italy.

Finasteride is a potent inhibitor of the enzyme steroid 5 alpha-reductase now approved as a drug for the treatment of benign prostatic hyperplasia. We describe an original method for the quantitative determination of finasteride at picogram level in human plasma by isotope-dilution gas chromatography mass spectrometry. 5,6,6-[2H3]Finasteride was synthesized with an high ratio of trideuteration (finasteride/[2H3]finasteride = 0.007) allowing its optimal use as internal standard. Plasma samples were purified in a single-step procedure on solid-phase extraction C18 columns with a recovery > or = 90%. Samples were injected in the GC-MS instrument without any derivatization and the minimum detection level of finasteride was 50 pg with a signal-to-noise ratio of 6:1. The coefficients of variation for the 5 and 10 ng/ml (plasma) concentrations were 5.8% and 4%, respectively. The method has been applied to the determination of the plasma pharmacokinetic of finasteride in five male volunteers treated with a single 5-mg dose of the drug, affording kinetic parameters which are in good agreement with the values previously reported with a different methodology. The present method results accurate, specific, sensible and reliable for a routinely determination of finasteride at picogram levels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8788149&dopt=Abstract finasteride Propecia



finasteride, Propecia
[Assessment of the effect of a 5-alpha-reductase inhibitor on cultured explants of human prostate]

[Article in Spanish]

Lopez Munnoz A, Larran Lopez J, Aparicio Patino J, Munoz de la Pascua MC, Salido Peracaula M, de Palacio Rubio ML, Romero Gutierrez L, Rodriguez Vallejoo JM.

Departamento de Anatomia Patologica y Biologia Celular. Facultad de Medicina. Universidad de Cadiz.

For the present work, cultures of hyperplastic human prostate explants were performed to evaluate the "in vitro" response of a 5-alpha reductase inhibitor-finasteride. Explants were cultured over a nine-week period in RPMI-1640 media supplemented with Penicillin-Streptomycin 4% and Fetal Bovine Serum 10%. Cultures were divided into one control group, one with testosterone added (1.25 x 10(4) micrograms/ml) and one which received testosterone (1.25 x 10(-4) micrograms/ml) plus finasteride (0,0038 mg/ml). Control explants showed involutive changes throughout the experience, which occurred later in those treated with testosterone and earlier and more marked in the case of finasteride. The testosterone-treated group showed intense positivity for PSA, a marker which reveals specific tissular functions, which remained uniformed in the control group through the entire experiment, and decreased gradually in the finasteride group. In summary, according to our work, culture of organs would be a useful tool for an in vitro evaluation of the hyperplastic human prostate response to the action of the 5-alpha reductase inhibitor, finasteride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8801791&dopt=Abstract finasteride Propecia



finasteride, Propecia
Effect of finasteride (Proscar) on the proliferation of cultured epithelial and stromal cells from normal and hyperplastic human prostates.

Lobaccaro JM, Boudon C, Lechevallier E, Mottet N, Rebillard X, Lumbroso S, Gibelin B, Sultan C.

Institut National de la Sante et de la Recherche Medicale, INSERM Unite 439, Montpellier, France.

Finasteride is a potent 5 alpha-reductase inhibitor which has proven useful in the clinical management of benign prostatic hyperplasia. To determine a potential mode of action for finasteride in prostatic cell proliferation, we have studied the incorporation of [3H]-thymidine into the DNA of cultured epithelial and stromal cells from normal and hyperplastic human prostates. The effects of short treatment with 10(-9) M and 10(-6) M finasteride (48 hrs.) on the incorporation of labelled thymidine were studied. A significant effect of finasteride on prostatic cell proliferation was observed at 10(-6) M for both epithelium and stroma from normal prostate: the rate of thymidine incorporation decreased to 80 +/- 3% (p < 0.001) and 55 +/- 10% (p < 0.01), respectively, compared to the control cells. As observed for normal prostates, this rate of thymidine incorporation was less for hyperplastic epithelium (70 +/- 4%, p < 0.001) than that observed for the hyperplastic stroma (74 +/- 4%, p < 0.01). These data clearly demonstrate that the reduction of the prostate volume observed in BPH treatment by finasteride is partly due to an inhibition of cell proliferation. However, the absence of complete inhibition of cell proliferation at 10(-6) M, a concentration known to strongly inhibit the 5 alpha-reductase activity, supports the hypothesis that factors other than DHT are necessary to induce prostatic cell proliferation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8828906&dopt=Abstract finasteride Propecia



finasteride, Propecia
FCE 28260, a new 5 alpha-reductase inhibitor: in vitro and in vivo effects.

Giudici D, Briatico G, Cominato C, Zaccheo T, Iehle C, Nesi M, Panzeri A, di Salle E.

Experimental Endocrinology Department, R&D Oncology, Pharmacia, Nerviano (MI), Italy.

FCE 28260 is a novel inhibitor of 5 alpha-reductase (5 alpha R), the enzyme responsible for the conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT). The compound caused inhibition of rat and human prostatic enzymes, with IC50 values of 15 and 16 nM, respectively, compared to the values of 30 and 52 nM shown by finasteride. Furthermore, FCE 28260 was highly potent in inhibiting human recombinant 5 alpha R type 2 and 1 isozymes, showing IC50 values of 3.3 and 36 nM, and therefore it was more potent than finasteride (IC50 values of 8.5 and 470 nM) on both isozymes. In prepubertal, T-implanted castrated rats, FCE 28260, given orally for 7 days, reduced ventral prostate growth with an ED50 of 0.8 mg/kg, i.e. five times lower than that shown by finasteride. No anti-androgenic activity in DHT-implanted castrated rats was found up to 10 mg/kg/day. In adult male rats, FCE 28260 reduced prostatic DHT concentrations 6 h after oral dosing with a potency similar to that of finasteride (65% reduction at 1 mg/kg) but was found to be markedly more potent than the reference compound at 24 h (74% reduction in prostate DHT at 10 mg/kg, compared to 26% reduction induced by finasteride). These results indicate that FCE 28260 represents a marked improvement over finasteride.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8836165&dopt=Abstract finasteride Propecia