Background: Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid5α-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case–control study was conducted with patients of Aichi Cancer Center Hospital.
and yeast alcohol dehydrogenase. The basis for this precipi- tation activity has not been defi ned thoroughly, but it may be due to the ability of certain polyphenols to form both numerous hydrogen bonds with a protein, as well as unselec- tive association of the aromatic nuclei of a polyphenol with certain amino acids, especially prolines. 40 5a-Reductase contains 14 (5.4%) proline residues; thus, this enzyme is not a proline-rich protein. Also, only 5 of these proline residues are in the carboxyl-terminal half of the protein containing the putative NADPH-binding site. From the results shown above, we see that the steroid 5a-reductase inhibitory activ- ity of condensed tannin comes from the binding to the steroid 5a-reductase, but not from the peroxide/superoxide or the precipitation of the steroid 5a-reductase protein. Also, the inhibitory activity of condensed tannin comes in part from its selective binding ability to the steroid 5a- reductase protein because the addition of other enzymes (SOD or catalase) to the assay system did not affect its inhibition of 5a-reductase (data not shown). In other words, the condensed tannin binds to the steroid 5a-reductase protein more selectively than SOD or catalase.
ies also suggested that higher serum concen- trations of testosterone and 3α-androstanediol glucuronide (3α-diol G) were associated with the increased risks of prostate cancer [7, 39]. The type II steroid5α-reductase enzyme is a critical enzyme in estrogen metabolism and it is exclusively expressed in the prostate; it is responsible for the conversion of progesterone (P) to the more potent androgen dihydrote- stosterone (DHT) in the prostate, which in turn binds to the androgen receptor, thus activating transcription of androgen receptor-responsive elements and inducing cellular proliferation .
by suppressing residual keloid fibroblasts on the margin of the wound to proliferate and deposit collagen. Similar results are achieved with 5α-oleandrin. Topical delivery of 5α-oleandrin is possible based on the physicochemical properties of 5α-oleandrin including its low molecular weight (576.72 Da) and lipid solubility . Although ir- ritant contact dermatitis caused by cutaneous exposure of oleander leaves has been reported , the allergenic properties have not been adequately studied. Generally, no positive patch test can be obtained . So, Clinical trials of this material either as a single therapy versus a
present in natural products (Tischler et al., 1988; Aiello et al., 1991; Pardo et al., 2000) and with proved utility as molecular probes for the study of aromatase inhibition (Numazawa & Tachibana, 1994; Pérez-Ornelas et al., 2005; Nagaoka & Numazawa, 2004). In fact, compound (I) is a synthetically valuable intermediate (Ehrenstein, 1939) of the biologically active androst-4-ene-3,6,17-trione compound, (Anthony et al., 1999) which is a well known aromatase inhibitor (Numazawa et al., 1987). Due to the interest of our group in the cytotoxic potential of steroids, a series of oxygenated steroids were further prepared and evaluated on HT-29 cancer cells (Carvalho et al., 2010a). Compound (I) showed no relevant cytotoxicity (IC 50 > 50µM), in contrast to cholestane-3β,5α,6β-triol and other cholestane derivatives.
Following our work on several androstane derivatives (Andrade et al. , 1999) as potential aromatase inhibitors and intermediates of their syntheses, the present study aims to contribute towards the elucidation of the different reactivities of the 5 α - and 5 β -androst-3-en-17-one, upon treatment with performic acid generated in situ in dichloromethane. The title compound, (I), was prepared from androst-4-ene-3,17-dione, through a modification of the McKenna process (McKenna et al. , 1959), as starting material for the synthesis of the potent and clinically useful antitumor steroid 4-hydroxy- androst-4-ene-3,17-dione (Tavares da Silva et al. , 1996) and its ring D modified derivative 4-hydroxy-17 a -oxa-17 a - homoandrost-4-ene-3,17-dione (Tavares da Silva et al. , 1997; Paixão et al. , 1998). The difference between the two epimers, 5 α and 5 β , is in the absolute configuration at C5. A 5 β -isomer would have a cis junction of rings A and B, the rings are fused trans in a 5 α -isomer. The X-ray analysis unequivocally establishes the molecular structure of (I) as an α configuration.
The molecule contains a fused four-ring system A/B/C/D. The A/B, B/C and C/D ring junctions are trans-fused. In the steroid nucleus, the cyclohexane rings (A, B and C) adopt chair conformations, whereas the cyclopentane ring (D) exhibits a half-chair form. The methylamino substituent is attached equatorially to ring A [C1ÐC2ÐC3ÐN1 = 174.9 (2) ] and the C24ÐN1ÐC3ÐC2 torsion angle of
Transurethral resection of the prostate (TURP) remains the gold standard for patients with benign prostatic hyperplasia (BPH) that failed medical therapy. Periopera- tive hemorrhage is one of the major complications of TURP, and prolonged bleeding will lead to blood trans- fusion and clot retention . 5α-Reductase inhibitors (5ARIs), including finasteride and dutasteride, can block the conversion of testosterone to dihydrotestosterone (DHT) and has been used to treat BPH and BPH-related hematuria .
Briefly, semi-confluent cells growing in T80 flasks were washed once with PBS for 5 minutes and replaced with 1ml of serum-free Optimem or RPMI medium containing ~ l|iC i of ^H-testosterone (1,2,6,7- ^H-testosterone) and made up to 20nM with cold T. A 2|il aliquot of this medium was taken and counted in a liquid scintillation counter to determine the amount of radioactivity added to each flask. The cells were incubated at 37°C for 1 hour whilst being gently rocked from side to side. Previous work in this laboratory has shown that T metabolism is linear during the first hour in BPH cell suspensions (Smith, thesis 1993). After this incubation period the medium was removed using Pasteur pipettes and placed in a sterile glass tube. To stop the reaction an equal volume of ethyl acetate containing ~500cpm of *"^C-DHT and ~25|ig of each trace steroid (T, DHT, Androstenedione, 3 a and 3|3-androstanediols) was added, the tubes capped and vortexed to mix. The samples were centrifuged at KXX) rpm for 10 minutes and the top organic layer containing the steroids was removed and placed in a sterile glass tube. The medium was extracted again with an equal volume of ethyl acetate and the top organic layer pooled with the first extract. The steroid extracts were evaporated to dryness under nitrogen gas and resuspended in 50|il of ethanol.
percentage of free PSA, PSA velocity, age-specific PSA ranges, complex PSA, and transition zone (TZ) PSAD [4-6]. However, none of these indexes has achieved satisfactory results ap- plicable to everyday clinical practice. The interpretation of PSA is even more complex in patients with benign prostatic hyperplasia who are administered 5α-reductase inhibitors (5ARIs). 5ARIs have been shown to reduce prostate volume (PV) by approximately 20% and to decrease serum PSA levels by about 50% on a 6-month course . It is generally accepted that the sensitivity and the specificity of serum PSA levels can be maintained by doubling the patient’s PSA value to account for the change in PSA . However, this is a rough estimation that does not exactly reflect the biological variability in PSA between individuals.
Androgen is reported to be a key factor in acne patho- genesis; especially, DHT in adulthood could induce bald- ing, prostate growth, and sebaceous gland activity . Furthermore, the activated sebaceous gland increases the production of sebum leading to blockage of the seba- ceous gland duct, causing acne. The enzyme 5α- reductase metabolizes testosterone to DHT, but abnor- mally high 5α-reductase activity results in excessive DHT production . .It is reported that caffeoyl deriva- tives from Adina rubella showed good 5α-reductase in- hibitory activity . In this experiment, CTL and TI inhibit androgen-induced sebum production by inhibit- ing the 5α-reductase reaction that produces DHT.
initially from diosgenin, for which the absolute configurations of all chiral centers of the steroid skeleton have been determined (Fieser & Fieser, 1959; Marker et al. , 1940). Recently, the absolute configurations of the chiral centres were confirmed by the X-ray crystal structure determination of a 3-Br substituted steroid substrate synthesized from diosgenin (Castro-Méndez et al. , 2002). The hydrogenation of 4-en-3-one moiety did not cause inversion of the configurations at C8, C9, C10, C13 and C14 (Throop & Tokes, 1967; House, 1972). Thus, by comparing the orientation of 5-H to that of methyl groups at C10 and C13, the absolute configuration of (I) could be determined.
Renal biopsy was performed after a diagnosis of steroid resistance, or if the patient’s age at onset of idiopathic nephrotic syndrome (INS) was more than 12 years. Repeat biopsy was performed if therapy toxicity was suspected. Biopsy specimens were processed using standard procedures that included hematoxylin-eosin, periodic acid-Schiff, and green Masson straining of formalin-included pieces. Immu- nofluorescence of frozen samples was carried out with a panel of antiserum protein antibodies against the immunoglobulins A, M and G (IgA, IgM, and IgG) and the 3rd and 4th complement components (C 3 and C 4 ).
Methods: A multi-centred, prospective observational study was conducted in paediatric nephrology OPD of two tertiary care hospitals in Kolkata over a period of 24 months. All consecutive children with diagnosed FRNS, SDNS and SRNS who were started on steroid sparing agents were enrolled and followed up for at least 6 months. Records of clinical examination, laboratory tests were collected and measured at the baseline and regular intervals. Safety parameters were noted and statistically analysed.
Inclusion Clinical diagnosis of heel pain and reporting pain and tenderness cantered on the medial tubercle of the calcaneum on weight bearing after rest which resolved partially or fully after activity. Exclusion Patients under the age of 18 yrs, pregnant females, steroid injection for heel pain in the previous 6 months, anticoagulant therapy, inability to give consent.