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| Author isozymes studied | Tissue type | Materials and methods | 5α-R1 | 5α-R2 | Notes |
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Eicheler et al. [10] 5α-R1-2 | Epidermis: genital (scrotum) nongenital (Axilla, breast, lip, eyelid) using a semiquantitative visual scale | Protein expression (IHC) using rabbit polyclonal antibodies against synthetic peptides from C-terminus parts of 5α-R1-2 proteins. Antibody sensitivity and specificity confirmed by ELISA and WB on FFPE biopsy or autopsy tissues | Nuclear, in epidermis from all sites: (scrotal> axilla> breast> lip> eye lid):
stratum basale (++), stratum spinosum (++), absent in stratum granulosum and stratum corneum, dermal papillae, fibrous and outer epithelial RS (++), inner epithelial RS (+), matrix cells of hair bulb (++), scrotal fibroblast (++), basal and secretory cells of sebaceous glands (++), secretory and myoepithelial cells of sweat glands (++), arrector pili muscles (+), dermal adipocytes (+). No qualitative differences in males and females | Cytoplasmic, in epidermis from all sites:
stratum spinosum (++), stratum basale (+), absent in stratum granulosum and stratum corneum, inner epithelial RS (++), matrix cells of hair bulb (+), absent in dermal papillae, fibrous and outer epithelial RS, basal (+) and glandular (−) cells of sebaceous glands, myoepithelial (+) and secretory cells (−) of sweat glands, dermal adipocytes (+)
No qualitative differences in males and females | 5α-R1 more uniformly spread in skin versus 5α-R2 that is mainly found in inner epith RS |
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Aumüller et al. [11] 5α-R1-2 | Many tissue types, using a semiquantitative visual scale | Protein expression (IHC) using rabbit polyclonal antibodies against synthetic peptides from C-terminus parts of 5α-R1-2 proteins. Antibody sensitivity and specificity confirmed by ELISA and WB.
Tissues from surgical pts and autopsies, fixed in Bouin's or formaldehyde | Mainly nuclear: Prostate: stroma (+), epithelium (+)
Seminal vesicle: stroma (+), epithelium (+)
Epididymis: stroma (+), epithelium (+)
Testis: Leydig cells (+), Sertoli cells (+)
Ovary: stroma (++), theca and granulosa cells (−)
Uterus: endometrium (+), myometrium (+)
Liver: hepatocytes (+/−), bile duct c (+), kupffer cells (++)
Pancreas: exocrine (+), islets of Langerhans (−)
Kidney: glomerulus (+), PT (−), DT (++), CD (+)
Adrenal: cortex (−), medulla (−)
Thyroid: thyrocytes (−), C cells (−)
Cerebral cortex: pyramidal c (+), glial cells (+/−)
Pituitary: prolactin cells (+), others (−) | Mainly cytoplasmic:
Prostate: stroma (+), epithelium (++), specially basal cells
Seminal vesicle.: stroma (+), epithelium (++)
Epididymis: stroma (+), epithelium (+)
Testis: spermatogonia (+), Leydig and Sertoli cell (−)
Ovary: stroma (+), theca and granulosa cells (+/−)
Uterus: endometrium (+), myometrium (+)
Liver: hepatocytes (++), bile duct c (+), kupffer cells (−)
Pancreas: exocrine (+), islets of Langerhans (−)
Kidney: glomerulus (−), PT (++), DT (+/−), CD (+)
Adrenal: ZG (+), ZF (+/−), ZR (+/−), med (−)
Thyroid: thyrocytes (−), C cells (−)
Cerebral cortex: pyramidal c (++), glial c (−)
Pituitary: prolactin cells (+), others (−) | 5α1-2 is ubiquitous |
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Bayne et al. [12] 5α-R1-2 | Scalp biopsies from bald and non-bald men | Protein expression (IHC) using validated mouse monoclonal antibodies against peptides from N-terminus parts of 5α-R1-2 and enzyme activity using 3H-T | In balding and non-balding scalp: 5α-R1 is expressed only in sebaceous glands
No expression was detected in hair follicles or in epidermis | In balding and nonbalding scalp: 5α-R2 is expressed in infundibula, outer (mainly) and inner epithelial RS of hair follicles.
No expression was detected in dermal papillae or in sebaceous glands | |
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Thigpen et al. [13] 5α-R1-2 | Autopsy and surgical tissue samples | Messenger RNA (NB) and protein expression (IHC and WB) using rabbit polyclonal antibodies against peptides from C-terminus parts of 5α-R1-2 | 5α-R1 protein is expressed in liver and chest skin and 5α-R1 mRNA was detected in cerebellum, hypothalamus, pons, medulla oblongata, skin, and liver 5α-R1 was not detected by WB in any fetal tissue.
5α-R1 was detected by WB in newborn liver, skin, and scalp.5α-R1 was detected by WB in all scalp samples from balding and nonbalding men (except one). It was not detected in any normal prostate, BPH, or PC sample | 5α-R2 protein is expressed in prostate, seminal vesicles, epididymis, and liver.
5α-R2 mRNA was detected in prostate, SV, epididymis. and liver. 5α-R2 was detected by WB only in fetal genital skin (not detected in fetal liver, adrenal, testis, ovary, scalp, and brain).
5α-R2 was detected by WB in newborn prostate, SV, epididymis, liver, skin. and scalp. 5α-R2 was not detected by WB in any sample of balding and nonbalding scalp from one man. It was detected in all normal prostate, BPH, and PC samples | 5α-R1 protein was not detected in any prostate sample |
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Thomas et al. [14] 5α-R1-2 | Prostate: BPH (TURP), ASCaP (RP), CaP metastasis in androgen deprivation-treated men (autopsy) | Protein expression (IHC) using rabbit polyclonal antibodies against peptides from N-terminus of 5α-R1-2 proteins.
Antibody specificity confirmed with WB on naïve, 5α-R1- and 5α-R2- transfected COS-1 cells and IHC on transfected COS-1 cells-Evaluated by measuring percentage of moderate- and high-intensity immunostaining areas in relation to total epithelial, PIN, or tumor area in PE tissues | Nuclear in BPH, shifts to cytoplasm in HGPIN and CaP
Immunostaining intensity: Metastasis> CR-CaP> AS-CaP = HGPIN> BPH | Mainly cytoplasmic in all specimens Immunostaining intensity:
BPH = Metastasis = CR-CaP> AS-CaP = HGPIN | All differences are statistically significant |
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Thomas et al. [14] 5α-R1-2 | Prostate: AS-CaP (RP) with Gleason score <7, 7, >7 | Protein expression (IHC) using validated rabbit polyclonal antibodies, evaluated by visually estimating percent of total tumor area showing low-, moderate, and high-intensity in relation to Gleason score | Mainly nuclear in BPH, nuclear and cytoplasmic in CaP (all grades), and in adjacent benign epithelial tissue Immunostaining intensity:
High grade > moderate grade = low grade > PC-adjacent benign tissue > BPH | Mainly cytoplasmic in all samples (benign and malignant) Immunostaining intensity:
BPH> high grade> moderate grade = low grade = adjacent benign tissue | Staining in CaP-adjacent benign tissue is not significanty different from low- and high-grade CaP for either isozyme |
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Söderstöm et al. [15] 5α-R1-2 | Prostate: BPH (TURP) and AS-CaP via RP or RC | Messenger RNA expression (sqRT-PCR) and measurement of 5α-R enzyme activity at pH 5.5 and 7 using 14C-T at 37°C
in homogenized frozen pulverized prostate tissue | 5α-R1 mRNA expression is similar in BPH and AS-CaP.
There was no correlation between enzyme activity at pH (5.5 and 7) and 5α-R1 mRNA expression as expressed on the basis of β-actin | 5α-R2 mRNA and enzyme activity were higher in BPH than in AS-CaP.
There was a positive correlation between enzyme activity at pH 5.5 and expression of 5α-R2 mRNA as expressed on the basis of β-actin | |
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Lehle et al. [61]
5α-R 1-2 | BPH and CaP tissue post prostate biopsy or RP frozen in liquid nitrogen, one human liver sample | Messenger RNA expression (ISH, sqRT-PCR) | ISH showed that 5α-R1 mRNA is expressed in epithelium > stroma mRNA expression levels by sqRT-PCR:
liver> CaP > BPH> Normal prostate | ISH showed that 5α-R2 mRNA is expressed in epithelium > stroma mRNA expression levels by sqRT-PCR:
liver = BPH > Normal prostate > CaP | |
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Habib et al. [16] 5α-R1-2 | BPH tissue (TURP) frozen in liquid nitrogen or in ice-cold RPMI with FBS and archival PE-BPH tissue | Messenger RNA expression (ISH, RT-PCR) and measurement of enzyme activity at pH 5 and 7.5 using 3H-T at 37°C in homogenized pulverized frozen prostate tissue | 5α-R1 mRNA expressed in epithelium > stroma | 5α-R1 mRNA expressed in epithelium > stroma
5α-R2 mRNA > 5α-R1 mRNA in BPH
5α-R2 enzyme activity ≫ 5α-R1 enzyme activity in homogenized BPH tissue | |
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Bonkhoff et al. [17] 5α-R1-2 | BPH (TURP), AS-CaP (RP), CR-CaP (channeling TUR) | Protein expression (IHC) using polyclonal rabbit antibodies against peptides from C-terminus parts of 5α-R1 and 2, validated by ELISA and WB | Mainly nuclear, in normal prostate and BPH tissue (luminal epithelial > basal) and in stroma 5α-R1 immunostaining > 5α-R2 in BPH (in both epithelium and stroma).
In CaP, 5α-R1 immunostaining became nuclear and cytoplasmic and more intense in HGPIN and CaP versus adjacent benign tissue (specially CR-CaP) | Mainly cytoplasmic (weak), in normal prostate and BPH tissue (basal > luminal epithelial) and stroma.
In CaP, 5α-R2 immunostaining became nuclear and cytoplasmic and more intense in HGPIN and CaP versus adjacent benign tissue (specially CR-CaP) | |
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Shirakawa et al. [18] 5α-R1-2 | BPH (RC) fixed in formaldehyde and paraffin-embedded | Messenger RNA (qRT-PCR), protein (IHC) expression using polyclonal rabbit antibodies against peptides from C-terminus parts of 5α-R1 and 2, validated by ELISA and enzyme activities at pH 5 and 7.5 using 3H-T at 37°C | 5α-R1 mRNA copy numbers> 5α-R2 mRNA in BPH
5α-R1 protein expression is intense in epithelium of BPH (higher than 5α-R2 protein)
5α-R1 enzyme activity at pH 7.5 is similar to 5α-R2 enzyme activity at pH 5.0 | 5α-R2 mRNA < 5α-R1 mRNA in BPH
5α-R2 protein expression is detected in epithelium and stroma of BPH (less intense than 5α-R1) | |
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Titus et al. [19] 5α-R1-2 | ASBP, AS-CaP and CR-CaP (RP or channeling TURP) tissue that was FFPE or snap frozen in liquid nitrogen | Protein expression (by IHC in TMAs that are quantified by visual scoring and digital image analysis and by WB) and enzyme activity in homogenized pulverized prostate tissue using 3H-ASD at 37°C | 5α-R1 is nuclear and cytoplasmic in all 3 tissues
Nuclear 5α-R1 staining intensity:
ASBP = AS-CaP = CR-CaP
Cytoplasmic 5α-R1 staining intensity:
ASBP = AS-CaP> CR-CaP
Not detected in stroma in any of the 3 tissues
In WB, 5α-R1 > 5α-R2 in all 3 tissues
5α-R1 enzyme activity > 5α-R2 in CR-CaP (3 folds) | 5α-R2 is mainly cytoplasmic in all 3 tissues
Nuclear 5α-R2 staining intensity:
ASBP = AS-CaP> CR-CaP Cytoplasmic 5α-R2 staining intensity:
ASBP = AS-CaP> CR-CaP
Not detected in stroma in any of the 3 tissues
In WB, 5α-R2 was undetectable in CR-CaP
5α-R2 activity > 5α-R1 in ASBP and AS-CaP | In all 3 tissues, expression of 5α-R1 is consistenty more than 5α-R2 (in nucleus) but similar in cytoplasm |
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Godoy et al. [20] 5α-R3 | Benign and malignant human tissue TMAs | Protein expression (IHC) using validated monoclonal mouse antibody against peptide from N-terminus of 5α-R3 protein and quantified by visual scoring and digital image analysis |
5α-R3 was mainly cytoplasmic
Benign tissue immunostaining: Kidney (PT,DT ++), liver (++), exocrine pancreas (++), skeletal muscle (+), skin (strata basale and spinosum ++), gastric epithelial cells (+), myometrium (++)
Malignant tissue: colon adenoCA (++), esophageal adenoCA (++), RCC (++), HCC (++), ovarian mucinous CA (++), stomach adenoCA (++), testis seminoma and YS tumor (++), thyroid papillary CA (++), endometrioid CA (++), breast CA (+)
ASBP: basal epithelial cells, HGPIN: benign basal and neoplastic epithelial cells, AS-CaP and CR-CaP: in neoplastic cells (5α-R3 immunostaining intensity: AS-CaP = CR-CaP > ASBP) | 5α-R3 protein expression ↑ in the cytoplasm of malignant cells versus benign cells in prostate, testis, thyroid, lung and breast CA |
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Yamana et al. [21] 5α-R3 | 20 benign human tissues, CaP, and breast cancer cell lines | 5α-R1-3 mRNA expression (RT-PCR) and measurement of 5α-R 1–3 enzyme activity using 14C-labelled ASD and T in intact cells in culture |
5α-R3 expression at the mRNA level is higher than 5α-R1 and 2 in frontal cortex, heart, colon, stomach, liver, pancreas, lung, BPH, prostate, testis, mammary gland, brain, cervix, ovary, dermis, epidermis, total skin, small intestine, spleen, and kidney
5α-R2 mRNA was the most abundant in BPH and muscle Finasteride inhibits 5α-R2 and 5α-R3 with similar potency (IC50 = 14.3 nM, 17.4 nM, resp.). Dutasteride is a more potent inhibitor of 5α-R3 than finasteride (IC50 = 0.33 nM) | 5α-R3 is ubiquitous Dutasteride is a triple 5α-RI in vitro |
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