Dihydrotestosterone Research Articles

Platelet-rich plasma therapy in the treatment of androgenic alopecia – review

Hair loss is a problem that affects many people around the world. Androgenic alopecia (AGA) is the most common cause of hair loss affecting up to 50% of men and 40% of women over the age of 50. This type of hair loss is mediated by androgens, the strongest of which is dihydrotestosterone (DHT). This hormone influences the weakening hair follicles. The problem of excess DHT and the associated androgenic hair loss may concern people practicing sports, especially aerobic disciplines of moderate and high intensity. In the recent decades, many topical and oral therapies have been introduced to delay and stop hair loss. However, commonly used medications have only a partial and temporary effect, therefore alternative treatment methods are needed. Platelet-rich plasma (PRP) is known, among other things, for its use in orthopedics. The use of PRP may benefit athletes in the treatment of injuries to tendons, ligaments, muscles and cartilage. Many publications indicate good results with the use of PRP in the treatment of hair loss.
 The aim of this study is to summarise the published reports on the effect of platelet-rich plasma (PRP) on hair loss prevention in people with androgenic alopecia (AGA) and to analyse the papers discussing androgen levels in physically active people.

PHLPP1 inhibits the growth and aerobic glycolysis activity of human ovarian granular cells through inactivating AKT pathway

BackgroundPolycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features, and PCOS is associated with infertility. PH domain Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) has been shown to regulate AKT. The aim of present study is to investigate the role of PHLPP1 in PCOS.MethodsThe expression levels of PHLPP1 in dihydrotestosterone (DHT)-treated human ovarian granular KGN cells were determined by qRT-PCR and Western blot. PHLPP1 was silenced or overexpressed using lentivirus. Cell proliferation was detected by CCK-8. Apoptosis and ROS generation were analyzed by flow cytometry. Glycolysis was analyzed by measuring extracellular acidification rate (ECAR).ResultsDHT treatment suppressed proliferation, promoted apoptosis, enhanced ROS, and inhibited glycolysis in KGN cells. PHLPP1 silencing alleviated the DHT-induced suppression of proliferation and glycolysis, and promotion of apoptosis and ROS in KGN cells. PHLPP1 regulated cell proliferation and glycolysis in human KGN cells via the AKT signaling pathway.ConclusionsOur results showed that PHLPP1 mediates the proliferation and aerobic glycolysis activity of human ovarian granular cells through regulating AKT signaling.

A decrease in serum dihydrotestosterone levels in 9-year-old Vietnamese children from a dioxin exposure area.

Dioxin is an environmental pollutant as well as an endocrine disruptor in humans. Our longitudinal study wants to clarify the relationship between dioxin exposure and endocrine disorders in children living in the Vietnamese dioxin hotspot. Seventeen congeners of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans (PCDDs/PCDFs) in maternal breast milk and seven serum steroid hormones in children of 43 and 46 mothers and their 9-year-old children from the non-exposure and the hotspot areas were measured, respectively. The steroid metabolic enzyme ratios were calculated based on the hormone level ratio. Most dioxin/furan congeners and toxic equivalents (TEQs) levels were significantly higher in the hotspot than in the non-exposure area, except for 2,4,7,8-TeCDF. The height and weight of girls from the hotspot area were substantially lower and inversely correlated with dioxin congener levels/total TEQs level dioxin. The dihydrotestosterone (DHT) levels in the hotspot were markedly lower than those in non-exposed in both genders. The cortisol concentrations were significantly higher in the hotspot than those from the non-exposure area only in the girls. The DHT/testosterone ratios that exhibited the 5α- or 5β-reductase activity declined by 50% in the hotspot area for both genders. The DHT levels showed strong inverse correlations with almost the PCDDs/PCDFs congeners and total TEQs dioxin in breast milk. This finding suggests that dioxin exposure in maternal breast milk might impact children's endocrine system until 9 years old, especially on the DHT biosynthesis.

Simultaneous determination of 18 steroids in the hypothalamic pituitary gonadal axis based on UPLC-MS/MS with multimode ionization.

To objectively quantify changes in steroid hormones in organisms caused by adverse environmental loads, we developed a simple and sensitive UPLC-MS/MS (ultra-performance liquid chromatography triple quadrupole mass spectrometry) method for the simultaneous determination of 18 steroid hormones on the HPG axis. This analytical method was based on liquid extraction and a multimode electrospray and atmospheric pressure chemical ionization (ESCi) source, which was optimized by mass spectrometry, liquid phase and pretreatment for the quantification of cholesterol (CH), aldosterone (A), cortisone (E), hydrocortisone (F), 21-deoxycortisol (21-DF), corticosterone (B), 11-deoxycortisol (11-DF), androstenedione (A2), estradiol (E2), estrone (E1), 2-methoxyestradiol (2-MeE2), 21-hydroxyprogesterone (21-OHP), 17-α hydroxyprogesterone (17α-OHP), testosterone (T), dehydroepiandrosterone (DHEA), progesterone (P4), dihydrotestosterone (DHT), and pregnenolone (P5). The method exhibits linearity in the analyte-concentration range 0.03-1000 μg mL-1 (r2 > 0.99), the spiked recoveries for the concentration range tested are 76.22-113.66%, and the relevant parameters of precision are 7.52-1.14%. Compared to other methods, this new method not only uses a small amount of serum (only 100 μL), but also permits the analysis of the challenging steroid, cholesterol. Furthermore, the method was successfully applied to the determination of steroids in Mus musculus, Carassius auratus, Rana catesbeiana Shaw, and Rana nigromaculata serum samples from randomly selected individuals. Therefore, this method is efficient and a very useful tool for assessing changes in steroid hormones.

The Clinical Use of Anabolic Steroid Oxandrolone for Burn Patients: A Review

To reduce burn damage, especially in severe cases, pharmacological interventions aiming to decrease the intense catabolism such as the use of anabolic androgenic steroids (AAS) have been previously studied. Oxandrolone, an oral derived compound from DHT (dihydrotestosterone), is used since the 60s, was pharmacologically developed to promote a predominance of anabolic action over androgenic action and is also approved by regulatory entities for on-label use in severe weight loss diseases. However, several published studies present differences in their methodologies (e.g. interventional or observational), patients characteristics, oxandrolone doses, usage protocols, clinical outcomes and magnitudes of observed effects. Therefore, we conducted a structured systematic search, in main scientific databases, searching for systematic reviews and meta-analysis that summarized the potential efficacy and safety of oxandrolone use in burn patients. A structured systematic search was carried out using a combination of MeSH terms for oxandrolone and burn, filtered for systematic reviews, in PUBMED and CENTRAL database. As a conclusion to the results that we observed (reduction in weight loss and a higher rate of weight regain after burns, a reduction in muscle mass loss, an improvement in muscle nitrogen retention and protein balance, a reduction in the healing time of the donor site, a reduction in the length of hospital stay, an increase in muscle strength, bone mass, total weight gain and growth rate), the clinical oxandrolone use for burn patients can be considered an effective and clinically safe pharmacological intervention and, given the important morphological and metabolic benefits observed in short and long-term, it should be routinely considered as an adjuvant treatment to be added to standard care in burn patients.

Berberine Protects Against Dihydrotestosterone-Induced Human Ovarian Granulosa Cell Injury and Ferroptosis by Regulating the Circ_0097636/MiR-186-5p/SIRT3 Pathway.

Polycystic ovarian syndrome (PCOS) is an endocrine syndrome in women of reproductive age. Berberine (BBR) is a Chinese herbal monomer that exhibits many pharmacological properties related to PCOS treatment. This study aims to analyze the effect of BBR on a cell model of PCOS and the underlying mechanism. Human ovarian granulosa (KGN) cells were treated with dihydrotestosterone (DHT) to mimic a PCOS cell model. The RNA expression of circ_0097636, miR-186-5p, and sirtuin3 (SIRT3) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blotting. Cell viability was analyzed by CCK-8 assay. Cell proliferation and apoptosis were investigated by 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry assay, respectively. The levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were analyzed by enzyme-linked immunosorbent assays (ELISAs). Fe2+ concentration was assessed by an iron assay kit. Oxidative stress was assessed by detecting reactive oxygen species (ROS) level and malondialdehyde (MDA) level using commercial kits. The association of miR-186-5p with circ_0097636 and SIRT3 was identified by dual-luciferase reporter assay and RNA pull-down assay. Circ_0097636 expression was downregulated in the follicular fluid of PCOS patients and DHT-treated KGN cells when compared with control groups. BBR treatment partially relieved the DHT-induced inhibitory effect on cell proliferation and promoted effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress in KGN cells. Additionally, circ_0097636 bound to miR-186-5p, and SIRT3 was identified as a target gene of miR-186-5p in KGN cells. BBR treatment ameliorated DHT-induced KGN cell injury by upregulating circ_0097636 and SIRT3 expression and downregulating miR-186-5p expression. Moreover, circ_0097636 overexpression protected KGN cells from DHT-induced injury by increasing SIRT3 expression. BBR ameliorated DHT-induced KGN cell injury and ferroptosis by regulating the circ_0097636/miR-186-5p/SIRT3 pathway.

ANTI-ALOPECIA ACTIVITY OF MORINGA (MORINGA OLEIFERA LAMK.) SEED OIL AGAINST DIHYDROTESTOSTERONE-INDUCED RABBITS

Objective: Alopecia is a condition where there is hair loss or no growth of hair, which can occur as a result of stress, heredity, hormonal factors or due to certain diseases such as diabetes mellitus. This study aimed to determine the anti-alopecia activity of moringa seed oil against rabbits induced by dihydrotestosterone (DHT).
 Methods: The methods used was the alopecia rabbit model according to Matias with moringa seed oil concentrations of 7.5, 10 and 12.5%, positive control (0.1% finasteride) and negative control (1% tween 80) with parameters hair length and hair weight test.
 Results: Results showed that moringa seed oil concentrations of 7.5, 10 and 12.5% had anti-alopecia activity with average hair length of 3.4±0.17, 3.9±0.20 and 4.5±0.28 cm, respectively and average hair weight of 118±23.148±30.9 and 175±47.2 mg respectively.
 Conclusion: Moringa seed oil concentration of 12.5% had optimal activity for developing as anti-alopecia based on the statistical analysis value of hair length (125x10-3>0.05) was not significantly different while hair weight (3x10-3<0.05) was significantly different from the positive control of 0.1% finasteride.

Troxerutin dampened hypothalamic neuroinflammation via microglial IL-22/IL-22R1/IRF3 activation in dihydrotestosterone-induced polycystic ovary syndrome rats

BackgroundPolycystic ovary syndrome (PCOS) is the most common reproductive-endocrine condition in premenopausal women. Troxerutin, a common clinical anti-coagulant agent, was shown to work as a strong IL-22 boosting agent counteracting the hyperactivated gonadotrophin releasing hormone (GnRH) neurons and heightened GnRH release, the neuroendocrine origin of PCOS with unknown mechanism in rats. Exploring the off-label use of troxerutin medication for PCOS is thus sorely needed. MethodsSerum IL-22 content and hypothalamic IL-22 protein were detected. Inflammatory factor levels in hypothalamo-pituitary were evaluated. Immunofluorescence staining was employed to determine the activation and M1/M2-prone polarization of microglia in arcuate hypothalamus and median eminence. RNA-sequencing and transcriptome analysis were applied to explore the potential driver of microglia M2-polarization in response to IL-22 bolstering effect. The function of microglial IL-22/IL-22R1/IRF3 system was further verified using in vivo knockdown of IL-22R1 and a potent IRF3 inhibitor in BV2 microglial cell lines in vitro. ResultsTroxerutin augmented serum IL-22 content, and its consequent spillover into the hypothalamus led to the direct activation of IL-22R1/IRF3 system on microglia, thereby promoted microglia M2 polarization in arcuate hypothalamus and median eminence, dampened hypothalamic neuroinflammation, inhibited hyperactive GnRH and rescued a breadth of PCOS-like traits in dihydrotestosterone (DHT) rats. The salutary effects of troxerutin treatment on hypothalamic neuroinflammation, microglial M1/2 polarization, GnRH secretion and numerous PCOS-like features were blocked by in vivo knockdown of IL-22R1. Moreover, evidence in vitro illustrated that IL-22 supplement to BV-2 microglia cell lines promoted M2 polarization, overproduction of anti-inflammatory marker and limitation of pro-inflammatory factors, whereas these IL-22 effects were blunted by geldanamycin, a potent IRF3 inhibitor. ConclusionHere, the present study reported the potential off-label use of troxerutin medication, a common clinical anti-coagulant agent and an endogenous IL-22 enhancer, for multiple purposes in PCOS. The rational underlying the application of troxerutin as a therapeutic choice in PCOS derived from its activity as an IL-22 memetic agent targeting the neuro-endocrine origin of PCOS, and its promotive impact on microglia M2 polarization via activating microglial IL-22R1/IRF3 system in the arcuate hypothalamus and median eminence of DHT female rats.

Establishment and characterization of matched immortalized human frontal and occipital scalp dermal papilla cell lines from androgenetic alopecia

Androgenetic alopecia (AGA), also known as male pattern baldness, is a common hair loss condition influenced by genetic and hormonal factors. Variations in gene expression and androgen responsiveness have been observed between the frontal and occipital regions of AGA patients. However, obtaining and cultivating frontal hair follicles is challenging. Therefore, no matched frontal and occipital dermal papilla (DP) cell lines have been reported yet. This study aimed to establish matched immortalized human frontal and occipital scalp DP cell lines from AGA patients. Simian virus 40 large T antigen (SV40T-Ag) and human telomerase reverse transcriptase (hTERT) were introduced into primary human DP cells. The obtained cell lines were characterized by assessing their gene expression patterns, androgen receptor (AR) levels, and the presence of 5-alpha reductase (5αR). Additionally, we examined their response to dihydrotestosterone (DHT) and evaluated cell viability. The conditioned medium from the frontal DP cell line inhibited human hair follicle growth, leading to reduced keratinocyte proliferation and increased apoptosis. Furthermore, when the cells were cultured in a 3D environment mimicking in vivo conditions, the 3D cultured frontal DP cell line exhibited weaker sphere aggregation than the occipital DP cell line due to the increased expression of matrix metalloproteinase 1 (MMP1), MMP3, and MMP9. Additionally, the expression of DP signature genes was inhibited in the 3D cultured frontal DP cell line. These matched frontal and occipital DP cell lines hold significant potential as valuable resources for research on hair loss. Their establishment allows us to investigate the differences between frontal and occipital DP cells, contributing to a better understanding of the molecular mechanisms underlying AGA. Furthermore, these cell lines may be valuable for developing targeted therapeutic approaches for hair loss conditions.

Cyanidin-3-O-glucoside and its derivative vitisin A alleviate androgenetic alopecia by exerting anti-androgen effect and inhibiting dermal papilla cell apoptosis

Androgenetic alopecia (AGA), one of the most common forms of hair loss, lacks satisfactory treatment methods in modern society. This study employed an experimental design combining in vitro and in vivo approaches to explore the effects of Cyanidin-3-O-glucoside (C3G) and Carboxypyranocyanidin-3-O-glucoside (Vitisin A) on AGA. In human dermal papilla cells (HDPCs), both anthocyanins demonstrated inhibitory effects on androgen receptors, significantly reduced dihydrotestosterone (DHT) induced apoptosis of HDPCs, and regulated the secretion of Fibroblast growth factor 7 and Transforming growth factor beta 1. In vitro transdermal experiment revealed that both C3G and Vitisin A could penetrate mice skin, aided by the application of cream. Furthermore, in vivo experiments with mice indicated that application of C3G or Vitisin A cream effectively improved hair follicles miniaturization, regression, and apoptosis caused by DHT. The repression of Wnt10b and β-catenin expression induced by DHT was prevented by C3G and Vitisin A in both cell and mouse model. Consequently, these findings suggest that C3G and Vitisin A could be considered as alternative methods for alleviating AGA.

Glucocorticoid Receptor Antagonism Improves Glucose Metabolism in a Mouse Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with obesity, insulin resistance, and dyslipidemia. Hyperandrogenism is a major characteristic of PCOS. Increased androgen exposure is believed to deregulate metabolic processes in various tissues as part of the PCOS pathogenesis, predominantly through the androgen receptor (AR). Notably, various metabolic features in PCOS are similar to those observed after excess glucocorticoid exposure. We hypothesized that glucocorticoid receptor (GR) signaling is involved in the metabolic symptoms of PCOS. In a PCOS model of chronic dihydrotestosterone (DHT) exposure in female mice, we investigated whether GR signaling machinery was (de)regulated, and if treatment with a selective GR antagonist alleviated the metabolic symptoms. We observed an upregulation of GR messenger RNA expression in the liver after DHT exposure. In white adipose tissues and liver we found that DHT upregulated Hsd11b1, which encodes for the enzyme that converts inactive into active glucocorticoids. We found that preventive but not therapeutic administration of a GR antagonist alleviated DHT-induced hyperglycemia and restored glucose tolerance. We did not observe strong effects of GR antagonism in DHT-exposed mice on other features like total fat mass and lipid accumulation in various tissues. We conclude that GR activation may play a role in glucose metabolism in DHT-exposed mice.

Abstract C061: The impact of the BRG1/BRM-associated factor (BAF) complex on the androgen receptor cistrome in African American prostate cancer

Abstract We aimed to establish in prostate cancer (PCa) how and why the androgen receptor displays differential functions in a manner driven by genomic ancestry, namely between African American (AA) and European American (EA) PCa, with the goal to assess how this may contribute to PCa health disparities. We utilized EA and AA non-malignant prostate and PCa cell models with confirmed genomic ancestry and defined the basal and dihydrotestosterone (DHT)-regulated AR and H3K27ac cistromes using CUT&RUN, and integrated these data with publicly available genomic counterparts. The DHT-dependent AR and H3K27ac cistromes significantly overlapped within AA cells and EA cells but there was significantly less overlap between AA and EA cells. For example, H3K27ac distributions were frequent (~15-20k sites) in each of non-malignant AA RC43N and EA HPr1AR, and malignant RC43T and LNCaP, and the significance of the overlaps were comparable for basal and DHT treated cells, but this was not significantly impacted by ancestry. By contrast the AR cistrome was highly DHT-dependent, with ~2k sites notably in LNCaP and RC43T, which very significantly overlapped with H3K27ac in the same cells but significantly less so across cells. Thus, although the H3K27ac cistrome was comparable across cells, the overlap with AR was driven by genomic ancestry. To investigate this, we focused on the BAF complexes as previously we identified reduced expression of a key component, SMARCA5, in AA PCa. These large multimeric complexes regulate nucleosome positioning during gene transcription and DNA repair. In PCa, the cBAF complex impacts different transcription factors, including ERG, and it is tempting to speculate that the corruption of cBAF identified in AA PCa phenocopies the impact of TMPRSS2-ETS impact observed in EA PCa. To test the possibility that the cBAF complex corrupts AR genomic functions in AA PCa we exploited scRNA-Seq data from PCa organoids from the Rb and Pten double knockout (PBCre4:Rb1f/f:Pten f/f ) to establish that expression of genes in the cBAF genes complex were collectively significantly altered in neuroendocrine PCa (NEPC) and Pouf23 androgen indifferent lineages. Secondly, knockdown of another cBAF component, SMARCC1, enhanced Enzalutamide sensitivity in same organoids. Finally, to test the impact of cBAF complex on AR signaling we have generated AA and EA PCa cell lines that stably express dCRISPR-activator (VP64) or repressor (KRAB) proteins and designed gRNAs to regulate expression of, for example, SMARCA5 and measure the impact on the AR cistrome and function. In summary, these findings identified that the shared AR and H3K27ac cistromes are driven by genomic ancestry, and that reduced expression of SMARCA5 and other components of the cBAF complex are significant in AA and advanced PCa, and impact AR signaling. Our future directions are focused on how SMARCA5 expression disrupts the balance between transcription factor functions, such as for the AR and other transcription factors, and effective DNA repair. Citation Format: Shahid S. Hussain, Debasis Nayak, David W. Goodrich, Clayton Yates, Moray Campbell. The impact of the BRG1/BRM-associated factor (BAF) complex on the androgen receptor cistrome in African American prostate cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C061.

PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome.

We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing's syndrome (CS) to define areas of dysregulated and druggable targets. Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing's disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1). Pathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc<-1.5) and related genes - FABP4 (l2fc<-5.5), PLIN1 (l2fc<-4.1) and ADIPOQ (l2fc<-3.3) - were significantly downregulated (p<0.005) in PBMAH. Significant downregulation of PPARG was also found in BADX-CD (l2fc<-1.9, p<0.0001) and CPA (l2fc<-1.4, p<0.0001). In vitro studies demonstrated that the PPARG activator rosiglitazone resulted in decreased cell viability in MUC1 and NCI-H295R (p<0.0001). There was also a significant reduction in the production of aldosterone, cortisol, and cortisone in NCI-H295R and in Dihydrotestosterone (DHT) in MUC1 (p<0.05), respectively. This therapeutic effect was independent of the actions of ACTH, postulating a promising application of PPARG activation in endogenous hypercortisolism.

Trazodone by epigenetic mechanism can reverse the post finasteride syndrome

The action mechanism of finasteride as inhibitor of the 5alpha-reductase enzyme in the brain could cause an epigenetic change imbalance in the messenger RNA of androgen receptor. The decrease of dihydrotestosterone (DHT) followed by an increase of free testosterone in the brain could in theory cause an imbalance in acetylation and methylation of histones in neurons. So, the post finasteride syndrome would be caused by an epigenetic change in androgen receptors of neurons circuits. Thus, the alpha-adrenergic antagonist properties of trazodone, for example cause priapism, and could change the epigenetic expression of androgen receptors in neuronal circuits responsible for erection and libido. Therefore, through this mechanism, the trazodone could reverse the effect of finasteride on the brain.

Ovarian nesfatin-1 in Hemidactylus flaviviridis: Reproductive phase-dependent expression, role and hormonal regulation

Nesfatin-1 has recently emerged as a modulator of ovarian functions in mammals. Studies in non-mammalian vertebrates, though limited and majorly restricted to fishes, have evidenced a role of this peptide in the regulation of ovarian steroidogenesis and oocyte maturation. Interestingly, nesfatin-1 remains completely unexplored in reptiles. Therefore, the present study aimed to identify nesfatin-1 and elucidate its role and regulation in the ovary of Hemidactylus flaviviridis. Ovarian expression of nucb2/nesfatin-1 was highest during late recrudescence and breeding while it was lowest during regression. Follicular stage-dependent expression analysis showed significantly high expression of nucb2/nesfatin-1 in previtellogenic follicles. Further, in vitro treatment of recrudescent wall lizard ovaries with nesfatin-1 resulted in increased expression of anti-apoptotic gene, bcl-2, along with a concomitant decline in the pro-apoptotic gene, caspase-3. In addition, proliferation/differentiation markers like scf, c-kit, pcna, and bmp-15 were stimulated in ovaries incubated with the peptide. Ovarian steroidogenesis was also positively influenced by nesfatin-1 as treatment with the peptide resulted in heightened star expression as well as increased estradiol and progesterone production. Also, all concentrations of nesfatin-1 stimulated glucose uptake and metabolism in wall lizard ovary. Our observations provide the first evidence of ovarian functions of nesfatin-1 in a reptile. Further, ovarian nucb2/nesfatin-1 was differentially regulated by gonadotropin and sex steroids wherein its expression was stimulated by dihydrotestosterone (DHT) and 17β-estradiol (E2) but inhibited by follicle-stimulating hormone (FSH). In summary, this is the first report of the presence, reproductive stage-dependent expression, role, and regulation of ovarian nucb2/nesfatin-1 in H. flaviviridis.

Analysis of Studies on the Role of Hormones in Micropenis Disorders: A Systematic Literature Review

A deep understanding of the role of specific hormones in genital development is key to designing effective therapeutic approaches. Factors such as testosterone deficiency, growth hormone disorders, or other hormonal imbalances can be targets for hormonal interventions that can affect penis size. This study aimed to explore the role of hormonal aspects in micropenis disorders. The literature search process was carried out on various databases (PubMed, Web of Sciences, EMBASE, Cochrane Libraries, and Google Scholar) regarding the role of hormonal aspects in micropenis disorders. This study follows the preferred reporting items for systematic reviews and meta-analysis (PRISMA) recommendations. Aspects of the hormonal role in micropenis include several key elements that influence the development of genital organs in men. Hormones, such as testosterone, growth hormone, estrogen, and dihydrotestosterone (DHT), play an important role in stimulating penis growth and development. Proper hormonal balance is necessary for normal genital development, and disturbances in the production of or response to these hormones may contribute to conditions such as micropenis.

DHT and Insulin Upregulate Secretion of the Soluble Decoy Receptor of IL-33 From Decidualized Endometrial Stromal Cells.

Interleukin 33 (IL-33) signaling regulates most of the key processes of pregnancy, including decidualization, trophoblast proliferation and invasion, vascular remodeling, and placental growth. Accordingly, dysregulation of IL-33, its membrane-bound receptor (ST2L, transducer of IL-33 signaling), and its soluble decoy receptor (sST2, inhibitor of IL-33 signaling) has been linked to a wide range of adverse pregnancy outcomes that are common in women with obesity and polycystic ovary syndrome, that is, conditions associated with hyperandrogenism, insulin resistance, and compensatory hyperinsulinemia. To reveal if androgens and insulin might modulate uteroplacental IL-33 signaling, we investigated the effect of dihydrotestosterone (DHT) and/or insulin on the expression of ST2L and sST2 (along with the activity of their promoter regions), IL-33 and sIL1RAP (heterodimerization partner of sST2), during in vitro decidualization of endometrial stromal cells from 9 healthy women. DHT and insulin markedly upregulated sST2 secretion, in addition to the upregulation of its messenger RNA (mRNA) expression, while the proximal ST2 promoter, from which the sST2 transcript originates, was upregulated by insulin, and in a synergistic manner by DHT and insulin combination treatment. On the other hand, sIL1RAP was slightly downregulated by insulin and IL-33 mRNA expression was not affected by any of the hormones, while ST2L mRNA expression and transcription from its promoter region (distal ST2 promoter) could not be detected or showed a negligibly low level. We hypothesize that high levels of androgens and insulin might lead to subfertility and pregnancy complications, at least partially, through the sST2-dependent downregulation of uteroplacental IL-33 signaling.

Changes in pituitary gonadotropin subunits and hypothalamic Kiss-1 gene expression by administration of sex steroids in ovary-intact female rats.

We examined how the sex steroids influence the synthesis of gonadotropins. The effects of sex steroids estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) in pituitary gonadotroph cell model (LβT2 cells) in vitro and ovary-intact rats in vivo were examined. The effects of sex steroids on Kiss1 gene expression in the hypothalamus were also examined in ovary-intact rats. In LβT2 cells, E2 increased common glycoprotein alpha (Cga) and luteinizing hormone beta (Lhb) subunit promoter activity as well as their mRNA expression. Although gonadotropin subunit promoter activity was not modulated by P4, Cga and Lhb mRNA expression was increased by P4. DHT inhibited Cga and Lhb mRNA expression with a concomitant decrease in their promoter activity. During the 2-week administration of exogenous E2 to ovary-intact rats, the estrous cycle determined by vaginal smears was disrupted. P4 or DHT administration completely eliminated the estrous cycle. Protein expression of all three gonadotropin subunits within the pituitary gland was inhibited by E2 or P4 treatment in vivo; however, DHT reduced Cga expression but did not modulate Lhb or follicle-stimulating hormone beta subunit expression. E2 administration significantly repressed Kiss1 mRNA expression in a posterior hypothalamic region that included the arcuate nucleus. P4 and DHT did not modulate Kiss1 mRNA expression in this region. In contrast, P4 administration significantly inhibited Kiss1 mRNA expression in the anterior region of the hypothalamus that included the anteroventral periventricular nucleus. The expression of gonadotropin-releasing hormone (Gnrh) mRNA in the anterior hypothalamic region, where the preoptic area is located, appeared to be decreased by treatment with E2 and P4. Our findings suggest that sex steroids have different effects in the hypothalamus and pituitary gland.

Association between Steroid Hormones and Insulin Resistance in Patients with Polycystic Ovary Syndrome

Objectives: Women with Polycystic Ovary Syndrome (PCOS) are more prone to adverse outcomes, including hypertension, obesity, hyperlipidemia, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. This study examined the potential link between abnormal steroid hormone levels and insulin resistance (IR) in reproductive-aged women with PCOS.&#x0D; Methods: This study involved 61 participants: a case group of 33 patients with confirmed PCOS based on Rotterdam criteria and a control group of 28 healthy individuals without PCOS. Steroid hormone levels, IR indices, metabolic markers, and demographic characteristics of participants were measured.&#x0D; Results: The results showed significant differences in testosterone (P=0.018), dihydrotestosterone (DHT) (P=0.009), and androstenedione (P=0.002) levels between the two groups. Insulin levels and HOMA-IR were significantly higher in the patients (P=0.034 and 0.025, respectively). Significant correlations were found between androstenedione and insulin (P=0.021), fasting blood sugar, and homeostatic model assessment of insulin resistance (HOMA-IR) levels (P=0.001), as well as between DHT level and IR indices (P=0.03). Additionally, patients with PCOS had higher diastolic blood pressure and lower levels of T4.&#x0D; Conclusion: The findings of this study showed higher androgen levels in PCOS patients and a significant correlation between DHT and androstenedione levels with IR indices in PCOS patients, which establishes a remarkable connection between hyperandrogenism and insulin resistance in PCOS.

Androgen signaling stabilizes genomes to counteract senescence by promoting XRCC4 transcription.

Aging is accompanied by a decreased DNA repair capacity, which might contribute to age-associated functional decline in multiple tissues. Disruption in hormone signaling, associated with reproductive organ dysfunction, is an early event of age-related tissue degeneration, but whether it impacts DNA repair in nonreproductive organs remains elusive. Using skin fibroblasts derived from healthy donors with a broad age range, we show here that the downregulation of expression of XRCC4, a factor involved in nonhomologous end-joining (NHEJ) repair, which is the dominant pathway to repair somatic double-strand breaks, is mediated through transcriptional mechanisms. We show that the androgen receptor (AR), whose expression is also reduced during aging, directly binds to and enhances the activity of the XRCC4 promoter, facilitating XRCC4 transcription and thus stabilizing the genome. We also demonstrate that dihydrotestosterone (DHT), a powerful AR agonist, restores XRCC4 expression and stabilizes the genome in different models of cellular aging. Moreover, DHT treatment reverses senescence-associated phenotypes, opening a potential avenue to aging interventions in the future.