5-alpha_reductase
The enzyme 5a-reductase is involved in the conversion of testosterone to the active form dihydrotestosterone (DHT). Androgenetic Alopecia (male pattern baldness) is increased by high levels of dihydrotestosterone, thus reducing the levels of dihydrotestosterone improves Androgenetic Alopecia.
Medications such as Finastiride are 5a-Reductase inhibitors of antiandrogenic activity and used in the treatment of Androgenetic Alopecia. These medications decrease the levels of available 5a-reductase prior to testosterone's binding with the enzyme thus reducing levels of dihydrotestosterone (DHT).
An excellent text on 5-alpha-reductase The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases is a good starting point to learn more.
Clinical Studies
| Clinical Studies | Abstract |
| Reduced Bone Mass and Muscle Strength in Male 5a-Reductase Type 1 Inactivated Mice. | Androgens are important regulators of bone mass but the relative importance of testosterone (T) versus dihydrotestosterone (DHT) for the activation of the androgen receptor (AR) in bone is unknown. 5a-reductase is responsible for the irreversible conversion of T to the more potent AR activator DHT. There are two well established isoenzymes of 5a-reductase (type 1 and type 2), encoded by separate genes (Srd5a1andSrd5a2). 5a-reductase type 2 is predominantly expressed in male reproductive tissues whereas 5a-reductase type 1 is highly expressed in liver and moderately expressed in several other tissues including bone. The aim of the present study was to investigate the role of 5a-reductase type 1 for bone mass using mice. Four-month-old male mice had reduced trabecular bone mineral density (236%, p,0.05) and cortical bone mineral content (215%, p,0.05) but unchanged serum androgen levels compared with wild type (WT) mice. The cortical bone dimensions were reduced in the male mice as a result of a reduced cortical periosteal circumference compared with WT mice. T treatment increased the cortical periosteal circumference (p,0.05) in orchidectomized WT mice but not in orchidectomized mice. Male mice demonstrated a reduced forelimb muscle grip strength compared with WT mice (p,0.05). Female mice had slightly increased cortical bone mass associated with elevated circulating levels of androgens. In conclusion, 5a-reductase type 1 inactivated male mice have reduced bone mass and forelimb muscle grip strength and we propose that these effects are due to lack of 5a-reductase type 1 expression in bone and muscle. In contrast, the increased cortical bone mass in female mice, is an indirect effect mediated by elevated circulating androgen levels. |
| Hormonal treatment of patients with benign prostatic hyperplasia: pros and cons. | The recognition that dihydrotestosterone is a "major player" in the development of benign prostatic hyperplasia (BPH) provided an impetus for the development of a 5a-reductase inhibitor, finasteride. During the past 5 years, a number of publications have noted that alpha blockers appear more efficacious than finasteride. This article reviews the role of hormones (particularly finasteride) in the treatment of lower urinary tract symptoms caused by BPH. These observations indicate that finasteride has a role in the management of larger prostates. Long-term use reduces the development of urinary retention and need for invasive procedures such as transurethral prostatectomy. The major adverse impact of finasteride is its effect on the patient's libido and sexual function. This is a less morbid problem for the elderly than the potential syncope associated with the use of alpha blockers. A greater understanding of the interaction of hormones on prostate receptors will provide newer tools for the treatment of BPH. |
| Advances in the treatment of male androgenetic alopecia: a brief review of finasteride studies. | Finasteride is a type 2 5a-reductase inhibitor and therefore mimics the biochemical profile of inherited type 2 5a-reductase deficiency in men. It was developed to grow hair in androgenetic alopecia and shrink benign prostatic hyperplasia. Various clinical trials of finasteride have confirmed its beneficial effects in androgenetic alopecia in males, but not in females. It can produce visible hair growth in up to 66% of men with mild to moderate alopecia, but importantly can stop hair loss in 91% of patients. In long-term finasteride studies, placebo patients were characterized by significant and progressive hair loss. It can be concluded that finasteride prevents further hair loss by actually continuing to grow enough hair to preserve scalp coverage. This is confirmed by the loss of hair following withdrawal of finasteride in such cases. The proven preservative effect of finasteride, in addition to its restorative effect, is a strong indication for prescribing it in early cases of androgenetic alopecia before much hair has been lost. |
| Enzymology of the hair follicle. | Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. This continuous process results in a type of alopecia that follows a definite pattern in those individuals who are genetically predisposed. A genetic predisposition is a feature of AGA, but the predisposing genes are still unknown. Our understanding, however, of the hormonal effects on hair growth is far move advanced, and human hair follicles are not only targets for androgens, but also reveal an active androgen metabolism, with the ability to convert several androgens by different steroidogenic enzymes. Recent results suggest that the dermal papilla of the hair follicle expresses abundant type 2 5a-reductase, 3b-HSD and steroid sulfatase activity. Therefore, current information about the androgen metabolism in hair follicles is reviewed and the potential impact on future therapeutic approaches is discussed. |