5α-reductase Activity Research Articles

PROCESS VALIDATION OF BETA-SITOSTEROL HAIR GEL FORMULATION AND EVALUATION OF 5 ALPHA REDUCTASE INHIBITION IN VITRO FOR THE TREATMENT OF ANDROGENETIC ALOPECIA

Objective: The present study was aimed to develop topical gel containing β-sitosterol using carbopol 940 as a gelling agent and to investigate 5 alpha reductase (5α-reductase) inhibitory activity of suitable gel formulation and compare it with a commercial product used topically for alopecia. Methods: Three different batches of β-sitosterol hair gel formulation were manufactured and evaluated. Additionally, the 5α-reductase inhibitory activity of the prepared formulation, finasteride as a positive control, was evaluated and compared to the commercial herbal formulation used. Results: According to the analytical findings of three different batches, the gel formulation is good in appearance, homogeneous, and easily spreadable. Based on findings from HPLC and HPTLC, the amount of β-sitosterol in those formulations complies with the label claim. By checking different critical parameters of those batches, we established the manufacturing process method validation and the process reproducibility. In vitro results showed the good 5α-reductase inhibitory potential of prepared gel formulation and then commercial product. The IC50 value of the prepared formulation was 118.960±0.634 (µg/ml) and standard beta-sitosterol 88.854±0.70 (µg/ml), whereas Finasteride (positive control) 224.372±3.103 (ng/ml). Conclusion: Thus, β-sitosterol formulation utilises a straightforward, low-cost production, less time-consuming process with minimal facility and equipment requirements. The formulation may be a promising candidate for future investigation into their antiandrogenic activities.

Assessment of the anti-hair loss potential of Camellia japonica fruit shell extract in vitro.

Hair loss is caused by various factors. Impacts of these factors are often overlapped and intensified. Currently, mitigation of hair loss is being studied by proliferating dermal papilla cells (DPCs) and inhibiting deleterious factors such as dihydrotestosterone (DHT) and oxidative stress on hair growth. Camellia japonica (C.japonica) fruit shell is a discarded part. Its biological activity remains to be elucidated. In this study, we investigated the capacity of C.japonica fruit shell extract (CJFSE) for hair loss mitigation. MTT assay, spheroid culture and quantitative RT-PCR were performed to observe the proliferative effect of CJFSE on hair follicle dermal papilla cells (HFDPCs). Effects of CJFSE on DHT-induced hair loss were confirmed by Dkk-1 ELISA, β-galactosidase (β-gal) and 5α-reductase activity assay. In addition, effects of CJFSE on oxidative stress were confirmed through DPPH and ROS production assays. CJFSE increased the proliferation and spheroid size of HFDPCs. Expression levels of VEGF-A, Wnt-1, c-Myc and Cyclin D1 were upregulated by CJFSE. CJFSE also suppressed 5α-reductase activity and DHT-induced decrease in cell proliferation, Dkk-1 secretion and β-gal activity. Moreover, CJFSE showed DPPH scavenging activity and ameliorated hydrogen peroxide-induced ROS production and β-gal activity. Finally, gallic acid and protocatechuic acid were observed in CJFSE through HPLC analysis. CJFSE has the potential to alleviate hair loss by promoting hair cell growth and suppressing effects of DHT and oxidative stress on hair.

Brassinosteroids is involved in methane-induced adventitious root formation via inducing cell wall relaxation in marigold

BackgroundMethane (CH4) and brassinosteroids (BRs) are important signaling molecules involved in a variety of biological processes in plants.ResultsHere, marigold (Tagetes erecta L. ‘Marvel’) was used to investigate the role and relationship between CH4 and BRs during adventitious root (AR) formation. The results showed a dose-dependent effect of CH4 and BRs on rooting, with the greatest biological effects of methane-rich water (MRW, CH4 donor) and 2,4-epibrassinolide (EBL) at 20% and 1 μmol L− 1, respectively. The positive effect of MRW on AR formation was blocked by brassinoazole (Brz, a synthetic inhibitor of EBL), indicating that BRs might be involved in MRW-regulated AR formation. MRW promoted EBL accumulation during rooting by up-regulating the content of campestanol (CN), cathasterone (CT), and castasterone (CS) and the activity of Steroid 5α-reductase (DET2), 22α-hydroxylase (DWF4), and BR-6-oxidase (BR6ox), indicating that CH4 could induce endogenous brassinolide (BR) production during rooting. Further results showed that MRW and EBL significantly down-regulated the content of cellulose, hemicellulose and lignin during rooting and significantly up-regulated the hydrolase activity, i.e. cmcase, xylanase and laccase. In addition, MRW and EBL also significantly promoted the activity of two major cell wall relaxing factors, xyloglucan endotransglucosylase/hydrolase (XTH) and peroxidase, which in turn promoted AR formation. While, Brz inhibited the role of MRW on these substances.ConclusionsBR might be involved in CH4-promoted AR formation by increasing cell wall relaxation.

Alteration in glucocorticoids secretion and metabolism in patients affected by cystic fibrosis.

Cystic fibrosis (CF) is an inherited syndrome associated with a mutation in a cystic fibrosis transmembrane conductance regulator gene, composed of exocrine gland dysfunction involving multiple systems that may result in chronic respiratory infections, pancreatic enzyme deficiency, and developmental disorders. Our study describes for the first time the urinary profile of glucocorticoid metabolites and the activity of the enzymes involved in the development and metabolism of cortisol in patients with CF, using a gas chromatography/mass spectrometry method. Data were obtained from 25 affected patients and 70 sex- and age- matched healthy volunteers. We have shown a general decrease in the activity of enzymes involved in the peripheral metabolism of cortisol, such as 11β-hydroxysteroid dehydrogenase type 2, 5α- and 5β-reductases. In contrast, the activity of 11β-hydroxysteroid dehydrogenase type 1, the enzyme that converts cortisone to cortisol, increased. Furthermore, our study found a significant decrease in glucocorticoid excretion in patients with CF. This may suggest adrenal insufficiency or dysregulation of the HPA axis and the development of peripheral mechanisms to counteract cortisol degradation in the case of reduced synthesis of glucocorticoids by the adrenal glands. Furthermore, the activity of 5α-reductase seems to be enhanced only through the backdoor pathway, especially when we taking into consideration 11β-hydroxyandrosterone/11β-hydroxyetiocholanolone ratio which has been shown to be the best differential marker for enzyme activity. CF impairs nutritional effects and energetic balance in patients; thus, our findings suggest the existence of adaptive mechanisms due to limited secretion of adrenal steroids and subsequent diminished amounts of their metabolites in urine. On the other hand, local control of cortisol availability is maintained by enhanced 11βHSD1 activity and its recovery from cortisone in organs and tissues which need this. Steroid hormone dysregulation might be another important factor in the course of CF that should be taken into account when planning an effective and comprehensive therapy.

Mifepristone blocks the anxiolytic- and antidepressant-like effects of allopregnanolone in male rats

Background Allopregnanolone (3α, 5α-tetrahydroprogesterone) is an inhibitory neurosteroid synthesized from progesterone via 5α-reductase activity in the brain and has anxiolytic, antidepressant, sedative, anticonvulsant, and analgesic activity. Altered levels of allopregnanolone cause anxiety, depression, premenstrual syndrome, and psychiatric disorders. Although allopregnanolone exerts most of its actions by modulating GABAA receptor, NMDA receptor, BDNF expression, and PXR activity, a recent study showed its effects are blocked by mifepristone on lordosis behavior which indicates the involvement of progestin or glucocorticoid receptors in the effects of allopregnanolone since mifepristone blocks both these receptors. However, whether these receptors are involved in acute anxiolytic or antidepressant-like effects is unknown. Methods Adult male Wistar rats were used to study whether the prior administration of mifepristone would alter the effects of allopregnanolone in the elevated plus maze (EPM) and forced swim test (FST) was evaluated. Results 10 mg/Kg dose of allopregnanolone increased percent open arm entries in the EPM, whereas 3 mg/Kg dose of allopregnanolone decreased percent immobility in the FST. Mifepristone administration resulted in a U-shaped response in the FST (with 1 mg/Kg, s.c., decreasing the immobility time) without significantly impacting the behavior in the EPM. In combination studies, mifepristone blocked the anxiolytic and antidepressant effects of allopregnanolone. Conclusion The current study provides evidence for the first time that progestin or glucocorticoid receptors are involved in the acute anxiolytic and antidepressant effects of allopregnanolone. Understanding the mechanism of action of allopregnanolone will help us design better therapeutic strategies to treat neuropsychiatric diseases such as depression and anxiety.

Microbial conversion of pregnenolone by some filamentous fungi

In this work, biotransformations of pregnenolone 1 by Ulocladium chartarum MRC 72584, Cladosporium sphaerospermum MRC 70266 and Cladosporium cladosporioides MRC 70282 have been reported. U. chartarum MRC 72584 only hydroxylated 1 at C-7β and hydroxylated 1 at either C-7β or C-14α, accompanied with a concurrent epoxidation from the β-face. The same fungus hydroxylated a small amount of 1 at both C-7 and C-14α, accompanied with a subsequent oxidation at C-7. 3β,14α-Dihydroxy-5β,6β-epoxypregnan-20-one 4 and 3β,7β-dihydroxy-5β,6β-epoxypregnan-20-one 5 obtained from the incubation of 1 with this fungus were determined as new metabolites. C. sphaerospermum MRC 70266 converted most of 1 into a 3-keto-4-ene steroid and independently hydroxylated it at C-6α, C-6β and C-7β. This fungus also hydroxylated 1 at C-7 and C-11α and then oxidized it at C-7. C. cladosporioides MRC 70282 converted almost half of 1 into a 3-keto-4-ene steroid. The same fungus reduced some of this 3-keto-4-ene steroid by a 5α-reductase activity while it hydroxylated the rest at C-6α and C-6β.

570 Targeting JAK/STAT and Wnt/b-catenin pathways and 5a-reductase activity to develop an effective anti-hair loss product

Androgenetic alopecia (AGA) is a multi-cause pathology resulting in hair cycle deregulation and production of short, fine hair. New insights into hair follicle biology and understanding of AGA have brought new strategies to treat it. The aim of this study was to demonstrate the interest of using ingredients targeting well-known and innovative biological targets to develop an effective anti-hair loss product. The active ingredients were evaluated on their ability to regulate the hair cycle. Activation of the Wnt/b-catenin pathway in hair follicle dermal papilla cells (HFDPC) was assessed using a reporter gene assay strategy. Inhibition of interleukine-6-induced JAK/STAT pathway activation in outer root sheath keratinocytes (ORSK) was assessed by measuring STAT3 phosphorylation. Conversion of testosterone (T) to DHT by the enzyme 5a-reductase (5aRed) in HFDPC was assessed by analysing T metabolism using radiolabelled T. A lotion containing these ingredients was tested on 60 subjects for 3 months, 2 applications per week for 1 month then 1 application per week for the following 2 months. The anagen/telogen (A/T) ratio was assessed by phototrichogram analysis. The combination of Nasturtium officinale and Tropaeolum majus extracts increased the activation of Wnt/b-catenin by 38% in HFDPC. Garcinia Mangostana extract significantly reduced JAK/STAT activation in ORSK by 33%. Glyceryl laurate significantly reduced T to DHT conversion by 42% suggesting that 5aRed activity was inhibited. When tested on 60 subjects, the lotion significantly increased the number of anagen hairs in subjects’ scalp and the A/T ratio, and also significantly decreased the number of telogen hairs after 3 months of treatment. Hair follicle biology is an ever-evolving science and targeting newly described biological pathways such as the JAK/STAT pathway with well-chosen ingredients will provide patients with effective anti-hair-loss solutions matching their needs and expectations.

Characterization of carotenoids in Lycium barbarum fruit by using UPC2-PDA-Q-TOF-MSE couple with deep eutectic solvents extraction and evaluation of their 5α-reductase inhibitory activity.

Carotenoids from Lyciu m barbarum fruits have possessed pharmacological efficacy against eye diseases, cardiovascular disorders, cancer, and benign prostatic hyperplasia. However, the efficient extraction, rapid characterization and activities evaluation of Lycium carotenoids remains a challenge. To concentrate and characterize Lycium carotenoids, we have developed ultrasound-assisted extraction methods with different deep eutectic solvents (DESs) and analyzed carotenoids by ultra-performance convergence chromatography coupled with photo diode array detector and quadrupole time-of-flight mass spectrometry (UPC2-PDA-Q-TOF-MSE). DESs containing choline chloride and malonic acid presented better extraction efficiency and were more environmentally friendly than other extraction methods. Carotenoids were more quickly profiled (in 11min) by UPC2 compared to by UPLC (in 35min), with seventeen main peaks were characterized in the MS fragmentation patterns. The in vitro 5α-reductase inhibitory activity of DESs extracts, fractions and components were subsequently assessed, and the predominant component zeaxanthin dipalmitate (ZD) exhibited potent inhibitory activity. Our study provides a chemical and pharmacological basis for the further development of potential new drugs based on Lycium carotenoids.

Health Benefits and Safety of Red Pigmented Rice (Oryza sativa L.): In Vitro, Cellular, and In Vivo Activities for Hair Growth Promoting Treatment

The hair growth-promoting activities of Thai native red (Sang-Yod-SY and Mun-Poo-MP) and black (Black glutinous-BG and Hom-Nil-HN) pigmented rice (Oryza sativa L.) extracts, including in vitro 5α-reductase inhibition, hair growth-promoting activity on human hair germinal matrix cells, and in vivo hair-cycle-converting activity in C3H/HeMlac mice, were investigated. Moreover, these extracts were determined to be safe via cytotoxicity (HaCaT cell) and in vivo irritation tests. The results showed that SY red rice extract with high contents of proanthocyanidin (1.50 ± 0.16 mgECE/g extract) exhibited significantly higher 5α-reductase inhibitory activity (18.5 ± 9.0 mgFEA/g extract) (p < 0.05). The maximum growth-promoting activity for human matrix cells treated with SY extract reached about 216.2 ± 0.7% (1 mg/mL) relative to control (100%) after 3 days culture (p < 0.05). Moreover, topical application of 1 mg/mL SY red pericarp rice extracts on shaven C3H skin in telogen phase led to significant hair regeneration (97.2 ±1.3%) based on the shaven area, while vehicle application only tended to yield a regeneration of 50.9 ± 11.7%. Red rice extracts were found to be safe, without signs of cytotoxicity and irritation. This research demonstrates the health benefits and safety of SY red pericarp extract when used for hair growing activity and its potential for use as a natural hair growth promoter and 5α-reductase inhibitor.

Synthesis, Characterization and Evaluation of 5α, 6β-Dihalo Androsterone Derivatives as 5α-Reductase Inhibitors

Background and Objective: Testosterone under the influence of 5α-reductase enzyme gets converted to dihydrotestosterone and high levels are found to be causative for androgen dependent disease like benign prostatic hyperplasia. Thus, 5α-reductase has been recognised as an important target for discovering new drugs against Benign Prostatic Hyperplasia and Prostate Cancer. Methods: In the present study, a series of 5α, 6β-Dichloro-17-Oxoandrostan-3β-yl esters (7a-7f) were synthesized and characterized by analytical and spectroscopic methods. The compounds were evaluated for their 5α-reductase inhibitory activity in-vivo by their effect on serum androgen level. Results: The target compounds (7a-7f) showed increased anti-androgenic activity as compared to finasteride and control, which implies that the target compounds are effective in inhibiting 5α-reductase. Particularly, compound 7b showing highest inhibitory activity and noteworthy D-Score was further sorted by performing solubility and dissolution studies. Results of these studies when compared with finasteride showed increased solubility and dissolution of target compound 7b. Conclusion: These results demonstrated that enhancement of activity by the presence of electronegative group at position 3 of the steroidal nucleus makes 7b a lead compound for further exploration and optimal formulation.

The Androgen Metabolome of Preterm Infants Reflects Fetal Adrenal Gland Involution

The human adrenal cortex changes with fetal-neonatal transition from the fetal to the adult organ, accompanied by changes in the steroid metabolome. As it is unclear how the observed developmental changes differ between preterm and full-term neonates, we investigated whether the involution of the fetal adrenals is following a fixed time course related to postmenstrual age or whether it is triggered by birth. Furthermore, the fetal and postnatal androgen metabolome of preterm infants was characterized in comparison to term babies. This was a prospective, longitudinal, 2-center study collecting spot urines of preterm and term infants during the first 12 to 18 months of life. Steroid metabolites were measured from spot urines by gas chromatography-mass spectrometry. Data relating were modeled according to established pre- and postnatal pathways. Fetal adrenal involution occurs around term-equivalent age in preterm infants and is not triggered by premature birth. Testosterone levels are higher in preterm infants at birth and decline slower until term compared to full-term babies. Dihydrotestosterone levels and the activity of the classic androgen biosynthesis pathway are lower in premature infants as is 5α-reductase activity. No difference was found in the activity of the alternate backdoor pathway for androgen synthesis. Human adrenal involution follows a strict timing that is not affected by premature birth. By contrast, prematurity is associated with an altered androgen metabolome after birth. Whether this reflects altered androgen biosynthesis in utero remains to be investigated.

Pumpkin Seed Oil-Loaded Niosomes for Topical Application: 5α-Reductase Inhibitory, Anti-Inflammatory, and In Vivo Anti-Hair Loss Effects.

Pumpkin seed oil (PSO)-loaded niosomes were prepared from Tween 20 and cholesterol by ethanol injection. Confocal microscopy showed better skin permeation and hair follicle accumulation of the niosomes compared to the PSO solution. The PSO-loaded niosomes inhibited 5α-reductase activity in DU-145 cells and hindered IL-6 activity in RAW 264.7 cells. These effects indicated the great potential of PSO-loaded niosomes to reduce hair loss. The hair scalp serum with PSO-loaded niosomes did not show irritation to reconstructed human skin. This formulation presented a significant decrease in the percentage of fallen hairs by 44.42% in the in vivo 60-second hair count experiment and a significant increase in the anagen to telogen (A/T) ratio (1.4-fold) in the TrichoScan® evaluation after 8 weeks of treatment compared to the initial conditions, indicating the promising efficacy of PSO-loaded niosomes as a natural alternative for anti-hair loss therapy.

Effects of some medicinal plant extracts on dermal papilla cells.

Miniaturization of the hair follicles is evident on the balding scalp. Approved medications, topical minoxidil, and oral finasteride for the treatment of alopecia sometimes come with undesirable adverse effects. The study was to examine the bioactivity of medicinal plants for finding the promising source of anti-hair loss application. Ten ethanolic extracts were prepared from Acacia concina (Willd.) DC., Acanthus ebracteatus Vahl, Bridelia ovata Decne, Cleome viscosa L., Cocos nucifera L., Hibiscus subdariffla L., Oryza sativa L., Terminalia chebula Retz., Tinospora crispa (L.) Hook. f. & Thomson and cytotoxic tested on dermal papilla cells using MTT assay. The effect of the extracts on cell cycle was also determined using flow cytometry technique. Anti-inflammatory activity was examined by determining IL-1β inhibition in RAW 257.4 cells. In vitro study of androgenic and 5α-reductase inhibitory activities were also determined using MTT assay and enzymatic reaction couple with liquid chromatography-mass spectrometry (LC-MS), respectively. Our results revealed that only A. ebracteatus promoted dermal papilla cell proliferation and the S and G2/M phases in cell cycle. A. ebracteatus also showed inhibitory activity against 5α-reductase and testosterone in reducing cell viability of the dermal papilla. Moreover, A. ebracteatus extract strongly inhibited LPS-stimulating IL-1β production in RAW 264.7 cells in a dose-dependent manner. Our finding indicated that the ethanolic extract of A. ebracteatus is a promising candidate for anti-hair loss treatment.

Steroid Hormone Profiling in Hyperandrogenism and Non-hyperandrogenism Women with Polycystic Ovary Syndrome.

The purpose of this study is to explore the differences in the steroid metabolic network between hyperandrogenic and non-hyperandrogenic women with polycystic ovary syndrome (PCOS). A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for the quantification of 36 kinds of serum steroids in 80 PCOS women during their follicular phase. Compared with those in non-hyperandrogenemia PCOS women (NA-PCOS), the levels of 17-hydroprogesterone (P = 0.009), androstenedione (P < 0.001), total testosterone (P < 0.001), dihydrotestosterone (P = 0.025), estrone (P = 0.007), and estradiol (P < 0.001) were increased in hyperandrogenemia PCOS (HA-PCOS) women. It was suggested that HA-PCOS may have increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P = 0.008), 3βHSD2 (androstenedione/dehydroepiandrosterone, P = 0.004), and 17βHSD3 (testosterone/dehydroepiandrosterone, P = 0.01) and decreased activity of 5α reductase (dihydrotestosterone/testosterone, P = 0.008). Moreover, the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH) was found to be related to these increased steroids and enzyme activities. In conclusion, the HA-PCOS and the NA-PCOS women showed different steroid profiles, and the different enzyme activities in steroidogenic pathway may be the main reason for the difference.

Increased systemic and adipose 11β-HSD1 activity in idiopathic intracranial hypertension.

ContextIdiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown etiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism is yet to be assessed.ObjectiveThe objective of this study was to determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype.DesignA retrospective case–control study and a separate exploratory analysis of a prospective randomized intervention study were carried out.MethodsThe case–control study compared female IIH patients to BMI, age, and sex-matched controls. In the randomized intervention study, different IIH patients were randomized to either a community weight management intervention or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilizing 24-h urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity.ResultsCompared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls.ConclusionThe study demonstrates that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point toward metabolic dysregulation as a feature of IIH.

Connarus semidecandrus Jack Exerts Anti-Alopecia Effects by Targeting 5α-Reductase Activity and an Intrinsic Apoptotic Pathway.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair–skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Role of glucocorticoid metabolism in childhood obesity-associated hypertension.

ObjectiveChildhood obesity is associated with alterations in hypothalamus–pituitary–adrenal axis activity. We tested the hypothesis that multiple alterations in the metabolism of glucocorticoids are required for the development of hypertension in children who become overweight.MethodsSpot urine for targeted gas chromatography-mass spectrometry steroid metabolome analysis was collected from (1) overweight/hypertensive children (n = 38), (2) overweight/non-hypertensive children (n = 83), and (3) non-overweight/non-hypertensive children (n = 56).ResultsThe mean (± s.d.) age of participants was 10.4 ± 3.4 years, and 53% of them were male. Group 1 and group 2 had higher excretion rates of cortisol and corticosterone metabolites than group 3 (869 (interquartile range: 631–1352) vs 839 (609–1123) vs 608 (439–834) μg/mmol creatinine × m2 body surface area, P < 0.01, for the sum of cortisol metabolites), and group 1 had a higher excretion rate of naive cortisol than group 3. Furthermore, groups differed in cortisol metabolism, in particular in the activities of 11β-hydroxysteroid dehydrogenases, as assessed from the ratio of cortisol:cortisone metabolites (group 2 < group 3), 5α-reductase (group 1 > group 2 or 3), and CYP3A4 activity (group 1 < group 2 or 3).DiscussionThe sequence of events leading to obesity-associated hypertension in children may involve an increase in the production of glucocorticoids, downregulation of 11β-hydroxysteroid dehydrogenase type 1 activity, and upregulation of 5α-reductase activity, along with a decrease in CYP3A4 activity and an increase in bioavailable cortisol.

Short-Term Fasting Attenuates Overall Steroid Hormone Biosynthesis in Healthy Young Women.

ContextFasting is stressful for the human body. It is managed by metabolic adaptations maintaining energy homeostasis and involves steroid hormone biosynthesis, but the exact interplay between energy and steroid metabolism remains elusive. Women with polycystic ovary syndrome (PCOS) suffer from disturbed metabolism and androgen excess, while in women with anorexia nervosa, cortisol and androgen production are decreased. By contrast, starvation of steroidogenic cells shifts adrenal steroid biosynthesis toward enhanced androgen production.AimThis study investigated the effect of fasting on steroid production in healthy women.MethodsTwenty healthy young women fasted for 48 hours; steroid profiles from plasma and urine samples were assessed at baseline, after 24 hours, and 48 hours by liquid and gas chromatography–mass spectrometry.ResultsFasting did not change overall steroidogenesis, although it increased progestogen production and lowered relative mineralocorticoid, glucocorticoid, and androgen production. The largest decrease in urine metabolites was seen for β-cortol, dehydroepiandrosterone, and androstenediol; higher levels were found for pregnanediol in urine and progesterone and aldosterone in serum. Activity of 17α-hydroxylase/17,20-lyase (CYP17A1), essential for androgen biosynthesis, was decreased after fasting in healthy women as were 21-hydroxylase (CYP21A2) and 5α-reductase activities. By contrast, hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) activity for cortisol inactivation seemed to increase with fasting.ConclusionSignificant changes in steroid metabolism occurred after 48 hours of fasting in healthy women. In contrast to metabolic changes seen at baseline in PCOS women compared to healthy women, and after starving of steroidogenic cells, no androgen excess was observed after short-term fasting in healthy young women.

Isolation and HPLC Quantitative Determination of 5α-Reductase Inhibitors from Tectona grandis L.f. Leaf Extract.

Steroid 5α-reductase plays a crucial role in catalyzing the conversion of testosterone to dihydrotestosterone, which is involved in many androgen-dependent disorders. Leaf-hexane extract from Tectona grandis L.f. has shown promise as a 5α-reductase inhibitor. The objectives of this current study were to isolate and identify 5α-reductase inhibitors from T. grandis leaves and to use them as the bioactive markers for standardization of the extract. Three terpenoid compounds, (+)-eperua-8,13-dien-15-oic acid (1), (+)-eperua-7,13-dien-15-oic acid (2), and lupeol (3), were isolated and evaluated for 5α-reductase inhibitory activity. Compounds 1 and 2 exhibited potent 5α-reductase inhibitory activity, while 3 showed weak inhibitory activity. An HPLC method for the quantitative determination of the two potent inhibitors (1 and 2), applicable for quality control of T. grandis leaf extracts, was also developed. The ethanolic extract showed a significantly higher content of 1 and 2 than found in the hexane extract, suggesting that ethanol is a preferable extraction solvent. This study is the first reported isolation of 5α-reductase inhibitors (1 and 2) from T. grandis leaves. The extraction and quality control methods that are safe and useful for further development of T. grandis leaf extract as an active ingredient for hair loss treatment products are also reported.

Ficus benghalensis as Potential Inhibitor of 5α-Reductase for Hair Growth Promotion: In Vitro, In Silico, and In Vivo Evaluation.

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro, in vivo, and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5α-reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5α-reductase II. The inhibition of 5α-reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5α-reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5α-reductase II and improved cell proliferation in rabbits. The statistical analysis (p < 0.05 or 0.01) and percentage inhibition (>70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle’s anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5α-reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss.