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Animals : An Open Access Journal From... Jun 2024Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in...
Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in the epididymal function of bucks. Twenty eleven-month-old Cashmere bucks were randomly divided into a control (CON) group and a bromocriptine (BCR, a prolactin inhibitor, 0.06 mg/kg body weight (BW)) treatment group. The experiment was conducted from September to October 2020 in Qinhuangdao City, China, and lasted for 30 days. Blood was collected on the last day before the BCR treatment (day 0) and on the 15th and 30th days after the BCR treatment (days 15 and 30). On the 30th day, all bucks were transported to the local slaughterhouse, where epididymal samples were collected immediately after slaughter. The left epididymis was preserved in 4% paraformaldehyde for histological observation, and the right epididymis was immediately preserved in liquid nitrogen for RNA sequencing (RNA-seq). The results show that the PRL inhibitor reduced the serum PRL and estradiol (E2) concentrations ( < 0.05) and tended to decrease luteinizing hormone (LH) concentrations ( = 0.052) by the 30th day, but no differences ( > 0.05) occurred by either day 0 or 15. There were no differences ( > 0.05) observed in the follicle-stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) concentrations between the two groups. The PRL receptor (PRLR) protein was mainly located in the cytoplasm and intercellular substance of the epididymal epithelial cells. The PRL inhibitor decreased ( < 0.05) the expression of the PRLR protein in the epididymis. In the BCR group, the height of the epididymal epithelium in the caput and cauda increased, as did the diameter of the epididymal duct in the caput ( < 0.05). However, the diameter of the cauda epididymal duct decreased ( < 0.05). Thereafter, a total of 358 differentially expressed genes (DEGs) were identified in the epididymal tissues, among which 191 were upregulated and 167 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that , , , , and were mainly enriched in the estrogen signaling pathway, steroid binding, calcium ion binding, the GnRH signaling pathway, the cAMP signaling pathway, and the chemical carcinogenesis-reactive oxygen species pathway, which are related to epididymal function. In conclusion, the inhibition of PRL may affect the structure of the epididymis by reducing the expression of the PRLR protein and the secretion of E2. , , , , and could be the key genes of PRL in its regulation of epididymal reproductive function.
PubMed: 38929397
DOI: 10.3390/ani14121778 -
Animals : An Open Access Journal From... Jun 2024MafB is a transcription factor that regulates macrophage differentiation. Macrophages are a traditional feature of the hamster Harderian gland (HG); however, studies...
MafB is a transcription factor that regulates macrophage differentiation. Macrophages are a traditional feature of the hamster Harderian gland (HG); however, studies pertaining to MafB expression in the HG are scant. Here, the full-length cDNA of the gene in hamsters was cloned and sequenced. Molecular characterization revealed that MafB encodes a protein containing 323 amino acids with a DNA-binding domain, a transactivation domain, and a leucine zipper domain. qPCR assays indicated that MafB was expressed in different tissues of both sexes. The highest relative expression levels in endocrine tissues were identified in the pancreas. Gonadectomy in male hamsters was associated with significantly higher mRNA levels in the HG; replacement with dihydrotestosterone restored mRNA expression. The HG in male hamsters contained twofold more MafB mRNA than the HG of female hamsters. Adrenals revealed similar mRNA relative expression levels during the estrous cycle. The estrous phase was associated with higher mRNA levels in the ovary. A significantly up-regulated expression and sexual dimorphism of MafB was found in the pancreas. Therefore, MafB in the HG may play an active role in the macrophage differentiation required for phagocytosis activity and intraocular repair. Additionally, sex steroids appear to strongly influence the MafB expression in the HG and pancreas. These studies highlight the probable biological importance of MafB in immunological defense and pancreatic β cell regulation.
PubMed: 38929347
DOI: 10.3390/ani14121728 -
Animals : An Open Access Journal From... Jun 2024The prostate is the only sexual gland of the male dog, and dihydrotestosterone (DHT) regulates its growth. In intact dogs, constant DHT stimulation results in benign...
The prostate is the only sexual gland of the male dog, and dihydrotestosterone (DHT) regulates its growth. In intact dogs, constant DHT stimulation results in benign prostatic hyperplasia (BPH) that can be treated with osaterone acetate (OSA). This study describes the effects of OSA treatment, detected by contrast-enhanced ultrasonography (CEUS), highlighting prostatic vascularization with a contrast agent composed of gas microbubbles. Fifteen dogs (2-8 years) of different sizes and breeds (4-30 kg) diagnosed with BPH are involved in the study. Before treatment (D), CPSE is measured (294.05 ± 115.97 ng/mL), and a B-mode ultrasound is performed (V = 2.80 ± 1.85), confirming BPH. CEUS highlights the length of the wash-in (11.93 ± 2.08 s) and wash-out (42.20 ± 6.99 s) phases of the contrast agent in the prostate and the presence of cysts and parenchymal alteration. Dogs are treated with OSA (0.5 mg/kg for 7 days) and reassessed after 21 days (D): CPSE and prostate volume are significantly ( < 0.001) reduced. The length of the wash-in (14.73 ± 2.54 s) and wash-out (51.13 ± 6.03 s) phases are significantly ( < 0.001) increased. The results confirm the effectiveness of the treatment, particularly the reduction in prostatic perfusion, confirmed by the increase in diffusion times of the contrast. Although preliminary, these findings are promising for the use of CEUS in monitoring dogs with BPH.
PubMed: 38891730
DOI: 10.3390/ani14111683 -
Communications Biology Jun 2024Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of...
Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Pten/PR mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Pten/PR mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.
Topics: Female; Endometrial Neoplasms; Humans; Animals; Mice; Forkhead Transcription Factors; Receptors, Androgen; Androgens; Cell Line, Tumor; Dihydrotestosterone; Gene Expression Regulation, Neoplastic; Middle Aged; Cell Proliferation
PubMed: 38890503
DOI: 10.1038/s42003-024-06433-w -
Steroids Jun 2024Occupancy of prostate cancer (PCa) cell androgen receptors (AR) signals proliferation, therefore testosterone biosynthesis inhibitors and AR antagonists are important...
In silico studies on the molecular interactions of steroid hormones and steroid hormone mimicking drugs in the androgen receptor binding cleft - Implications for prostate cancer treatment.
Occupancy of prostate cancer (PCa) cell androgen receptors (AR) signals proliferation, therefore testosterone biosynthesis inhibitors and AR antagonists are important PCa treatments. Conversely, androgen mimics (e.g., prednisone) used in management of PCa might cause proliferation. The balance between PCa proliferation and inhibition predicts treatment success. We used in silico molecular modelling to explore interactions between ARs, androgens (testosterone, dihydrotestosterone (DHT)) and drugs used to treat (bicalutamide) and manage (dexamethasone, prednisone, hydrocortisone) PCa. We found that hydrogen (H-) bonds between testosterone, DHT and Arg752, Asn705 and Thr877 followed by ligand binding cleft hydrophobic interactions signal proliferation, whereas bicalutamide antagonism is via Phe764 interactions. Hydrocortisone, dexamethasone and prednisone H-bond Asn705 and Thr877, but not Arg752 in the absence of a water molecule. Studies with a bicalutamide agonist AR mutation showed different amino acid interactions, indicating testosterone and DHT would not promote proliferation as effectively as via the native receptor. However, hydrocortisone and bicalutamide form Arg752 and Asn705 H-bonds indicating agonism. Our results suggest that as PCa progresses the resulting mutations will change the proliferative response to androgens and their drug mimics, which have implications for the treatment of prostate cancer.
PubMed: 38889811
DOI: 10.1016/j.steroids.2024.109456 -
Frontiers in Pharmacology 2024Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our...
Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%-90% as effective as VEGF in the stimulation of neovascularization in models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson's trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%-90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established.
PubMed: 38887556
DOI: 10.3389/fphar.2024.1370833 -
Frontiers in Aging Neuroscience 2024Taurine, an amino acid abundantly found in the brain and other tissues, has potential neuroprotective properties. Alzheimer's disease (AD) is a commonly occurring type...
BACKGROUND
Taurine, an amino acid abundantly found in the brain and other tissues, has potential neuroprotective properties. Alzheimer's disease (AD) is a commonly occurring type of dementia, which becomes more prevalent as people age. This experiment aimed to assess the neuroprotective effects of taurine on SH-SY5Y cells by examining its impact on Dihydrotestosterone (DHT), Dihydroprogesterone (DHP), as well as the expression of miRNA-21 and miRNA-181.
METHODS
The effects of various taurine concentrations (0.25, and 0.75 mg/mL), and LPS (0.1, and 12 mg/mL) on the SH-SY5Y cell line were assessed using the MTT assay. The levels of DHT and DHP were quantified using an ELISA kit. Additionally, the expression levels of miRNA-181 and miRNA-21 genes were examined through Real-Time PCR analysis.
RESULTS
The results of the MTT assay showed that treatment with taurine at concentrations of 0.25, and 0.75 mg/mL reduces the toxicity of LPS in SH-SY5Y cells. ELISA results indicated that taurine at a concentration of 0.25, and 0.75 mg/mL significantly elevated DHT and DHP hormones in the SH-SY5Y cell line compared to the untreated group ( < 0.01). The expression levels of IL-1β and IL-6 were decreased under the influence of LPS in SH-SY5Y cells after taurine treatment (p < 0.01). Gene expression analysis revealed that increasing taurine concentration resulted in heightened expression of miRNA-181 and miRNA-21, with the most significant increase observed at a concentration of 0.75 mg/mL ( < 0.001).
CONCLUSION
Our study findings revealed that the expression of miRNA-181 and miRNA-21 can be enhanced by taurine. Consequently, exploring the targeting of taurine, miRNA-181, and miRNA-21 or considering hormone therapy may offer potential therapeutic approaches for treating AD or alleviating severe symptoms. Nonetheless, in order to fully comprehend the precise mechanisms involved, additional research is required.
PubMed: 38867846
DOI: 10.3389/fnagi.2024.1379431 -
Frontiers in Physiology 2024In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are...
In addition to loss of sensory and motor function below the level of the lesion, traumatic spinal cord injury (SCI) may reduce circulating steroid hormones that are necessary for maintaining normal physiological function for extended time periods. For men, who comprise nearly 80% of new SCI cases each year, testosterone is the most abundant circulating sex steroid. SCI often results in significantly reduced testosterone production and may result in chronic low testosterone levels. Testosterone plays a role in respiratory function and the expression of respiratory neuroplasticity. When testosterone levels are low, young adult male rats are unable to express phrenic long-term facilitation (pLTF), an inducible form of respiratory neuroplasticity invoked by acute, intermittent hypoxia (AIH). However, testosterone replacement can restore this respiratory neuroplasticity. Complicating the interpretation of this finding is that testosterone may exert its influence in three possible ways: 1) directly through androgen receptor (AR) activation, 2) through conversion to dihydrotestosterone (DHT) by way of the enzyme 5α-reductase, or 3) through conversion to 17β-estradiol (E2) by way of the enzyme aromatase. DHT signals via AR activation similar to testosterone, but with higher affinity, while E2 activates local estrogen receptors. Evidence to date supports the idea that exogenous testosterone supplementation exerts its influence through estrogen receptor signaling under conditions of low circulating testosterone. Here we explored both recovery of breathing function (measured with whole body barometric plethysmography) and the expression of AIH-induced pLTF in male rats following C2-hemisection SCI. One week post injury, rats were supplemented with either E2 or DHT for 7 days. We hypothesized that E2 would enhance ventilation and reveal pLTF following AIH in SCI rats. To our surprise, though E2 did beneficially impact overall breathing recovery following C2-hemisection, both E2 supplementation and DHT restored the expression of AIH-induced pLTF 2 weeks post-SCI.
PubMed: 38803364
DOI: 10.3389/fphys.2024.1390777 -
Wellcome Open Research 2023Five-alpha reductase inhibitors (5ARIs) are used in the management of benign prostatic hyperplasia (BPH). 5ARIs prevent the conversion of testosterone to...
Five-alpha reductase inhibitors (5ARIs) are used in the management of benign prostatic hyperplasia (BPH). 5ARIs prevent the conversion of testosterone to dihydrotestosterone, which is important in prostate development. It has been suggested that 5ARIs can be used a chemopreventative agent for prostate cancer. The aim of this study was to assess the risk of prostate cancer associated with 5ARI use among men with BPH. Using Clinical Practice Research Datalink (CPRD) from 1992 to 2011 in UK, prostate cancer risk was retrospectively compared in men with a new diagnosis of BPH, with no history of prostate cancer who were treated with 5ARIs, to men treated with alpha blockers (ABs) and those given no pharmacological treatment. Incidence rate of prostate cancer was calculated by treatment group; the association between BPH treatment group and prostate cancer was estimated by a multivariate Cox model. 77,494 men with newly diagnosed BPH were included. The crude incidence rate of prostate cancer was 892.4 cases per 100,000 person-years amongst those treated with 5ARIs, compared with 1209.0 and 1542.9 in those treated with ABs and untreated individuals, respectively. The HR adjusted for potential confounders was 0.79 (0.72-0.86) for 5ARI vs ABs and 0.72 (0.66-0.79) for 5ARI vs untreated. After excluding the first year after BPH diagnosis, adjusted HRs attenuated to 0.87 (0.79-0.97) for 5ARI vs ABs and 0.97 (0.87-1.08) for 5ARI vs untreated. Among men diagnosed with BPH, we found evidence of lower risks of subsequent prostate cancer in those treated with 5ARIs, but this appeared to be driven by cases diagnosed within a year of BPH, possibly reflecting prevalent prostate cancers that were initially misdiagnosed. After excluding the first year after BPH diagnosis, there was little evidence of a reduced prostate cancer risk in those taking 5ARIs.
PubMed: 38774490
DOI: 10.12688/wellcomeopenres.19566.1