Hormone Administration Research Articles

Growth hormone therapy in Turner Syndrome (TS): A focused review on glucose metabolism outcomes

Introduction: Turner Syndrome (TS) patients inherently possess a higher risk of developing glycemic abnormalities due to their unique genetic makeup, and the administration of growth hormone (GH) therapy, while beneficial for growth, might exacerbate this tendency towards disturbed glucose metabolism. Objective of the Review: To evaluate the existing literature on the effects of GH therapy on glucose metabolism in TS patients, highlighting the balance between therapeutic benefits and potential metabolic risks. Methods: This review scrutinizes studies published from 2000 to 2024, focusing on the outcomes related to glucose metabolism in TS individuals undergoing GH therapy, encompassing aspects like insulin sensitivity, glucose tolerance, and metabolic health. Results: Insulin Sensitivity and Resistance: Initial findings suggest that GH therapy may exacerbate insulin resistance and elevate insulin levels, although these effects appear transient and potentially reversible after the cessation of therapy. Long-term Metabolic Outcomes: Later studies indicate that long-term GH therapy may lead to an improvement in insulin sensitivity and a normalization of carbohydrate metabolism, particularly after the therapy is discontinued. Variable Impacts on Glucose Tolerance: The reviewed literature shows mixed effects on glucose tolerance, with some studies reporting no significant changes, while others highlight a potential risk for worsening glucose metabolism. Body Composition and Metabolic Profile: Positive changes in body composition and lipid profiles were noted, which could confer metabolic benefits, yet the therapy's role in increasing insulin levels warrants careful consideration. Individual Variability and Monitoring Needs: The diverse responses to GH therapy underscore the necessity for individualized treatment plans and diligent metabolic monitoring to mitigate potential risks and optimize therapeutic outcomes. Conclusion: The administration of GH therapy in TS requires a delicate balance, considering its potential to both benefit and pose risks to glucose metabolism. Tailored monitoring and a comprehensive understanding of the individual patient’s metabolic response are essential for maximizing the therapy's efficacy while minimizing associated metabolic complications.

Sciatic endometriosis: Insights from imaging and personalized treatment

This outstanding image article delves into the intriguing instance of a 42-year-old woman grappling with persistent lumbosacral pain over 13 years, accentuated postpartum. Electromyography (EMG) and magnetic resonance imaging (MRI) uncovered sciatic endometriosis. The rarity of this manifestation prompted a biopsy for anatomopathological confirmation, underscoring the complexity of the case. Despite unsuccessful attempts with various interventions, the administration of gonadotropin-releasing hormone (GnRH) analogs led to significant improvement, emphasizing the efficacy of tailored treatments for uncommon endometriosis presentations. This case underscores the pivotal role of advanced imaging, particularly MRI, in precise diagnosis and personalized treatment planning, showcasing the transformative impact of well-tailored interventions on the intricate facets of endometriosis. The collaborative efforts of medical professionals, guided by imaging insights, not only alleviate symptoms but also contribute substantially to preserving neurological integrity, emphasizing the profound importance of tailored treatment in enhancing overall well-being.

Effects of thyroxin and luteinizing hormone releasing hormone on reproductive physiology of Rohu (Labeo rohita): Insights into spawning performance, oocyte maturation, steroidogenesis, and follicular development genes

As the global aquaculture industry grows, attention is increasingly turning towards assisted reproductive technologies. In this study, we examined the impact of D-Ala6, Pro9-Net-mGnRH (LHRHa: 0.4 mL/kg) and two doses (1 and 10 μg/kg fish) of thyroxin (T4) administered through a single injection on oocyte maturation, spawning performance, sex steroid hormone levels, as well as the expression of genes related to steroidogenesis and follicle development (ZP2, Cyp19a1a and SF-1) in Rohu (Labeo rohita). The study found that untreated female Rohu did not spawn, while those treated with LHRHa and thyroxin ovulated and spawned across a hormonal gradient. The highest spawning success was observed with a thyroxin dosage of 10 µg/kg (no significant change with a dose of 1 μg/kg), and female latency period decreased with increasing dosage. Additionally, females treated with thyroxin exhibited significantly higher fecundity than other experimental groups. Treatment with LHRHa and two doses of thyroxin significantly increased the gonadal somatic index compared to the control and sham groups. Hormonal treatment also led to increased fertilization success, hatching rate, and larval survival. At 12 h post-injection, females treated with thyroxin exhibited a significant decline in estradiol levels and expression of Zp2, Cyp19a1a, and SF-1 compared to other experimental groups. Levels of DHP significantly increased across the hormonal gradient. Histological analyses supported a steroidogenic shift, where oocyte maturation was accelerated by hormone administration, particularly with both doses of thyroxin. In conclusion, the findings suggest that thyroxin is a recommended treatment for assisted reproduction of Rohu due to its ability to induce spawning, increase fecundity and improve larval survival.

Estradiol modulates changes in effective connectivity in emotion regulation networks

Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So far, the neural underpinnings of the effect of E2 on emotional experience have been investigated using task-based functional magnetic resonance imaging (fMRI) and functional connectivity. In the present study, we examined whether the intrinsic network dynamics at rest (i.e., directed effective connectivity) related to emotion regulation are (1) modulated by E2 levels and (2) linked to behavioral emotion regulation ability. Hence, 29 naturally cycling women participated in two resting-state fMRI scans in their early follicular phase after being administered a placebo or an E2 valerate, respectively. Emotion regulation ability was assessed using a standard emotion regulation task in which participants were asked to down-regulate their emotions in response to negative images. The regions of two functionally predefined neural networks related to emotional down-regulation and reactivity were used to investigate effective connectivity at rest using spectral dynamic causal modelling. We found that E2, compared to placebo, resulted in changes in effective connectivity in both networks. In the regulation network, prefrontal regions showed distinct connectivity in the E2 compared to the placebo condition, while mixed results evolved in the emotional reactivity network. Stepwise regressions revealed that in the E2 condition a connection from the parietal to the prefrontal cortex predicted regulation ability. Our results demonstrate that E2 levels influence effective connectivity in networks underlying emotion regulation and emotional reactivity. Thus, E2 and its potential modification via hormonal administration may play a supporting role in the treatment of mental disorders that show a dysregulation of emotions.

Efficacy of Human Recombinant Growth Hormone in Females of a Non-Obese Hyperglycemic Mouse Model after Birth with Low Birth Weight.

We examined whether the administration of growth hormone (GH) improves insulin resistance in females of a non-obese hyperglycemic mouse model after birth with low birth weight (LBW), given that GH is known to increase muscle mass. The intrauterine Ischemia group underwent uterine artery occlusion for 15 min on day 16.5 of gestation. At 4 weeks of age, female mice in the Ischemia group were divided into the GH-treated (Ischemia-GH) and non-GH-treated (Ischemia) groups. At 8 weeks of age, the glucose metabolism, muscle pathology, and metabolome of liver were assessed. The insulin resistance index improved in the Ischemia-GH group compared with the Ischemia group (p = 0.034). The percentage of type 1 muscle fibers was higher in the Ischemia-GH group than the Ischemia group (p < 0.001); the muscle fiber type was altered by GH. In the liver, oxidative stress factors were reduced, and ATP production was increased in the Ischemia-GH group compared to the Ischemia group (p = 0.014), indicating the improved mitochondrial function of liver. GH administration is effective in improving insulin resistance by increasing the content of type 1 muscle fibers and improving mitochondrial function of liver in our non-obese hyperglycemic mouse model after birth with LBW.

Methods to accelerate fracture healing - a narrative review from a clinical perspective.

Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors. Fracture healing usually takes several weeks to months, during which patients are frequently immobilized and unable to work. As immobilization is associated with negative health and socioeconomic effects, it would be desirable if fracture healing could be accelerated and the healing time shortened. However, interventions for this purpose are not yet part of current clinical treatment guidelines, and there has never been a comprehensive review specifically on this topic. Therefore, this narrative review provides an overview of the available clinical evidence on methods that accelerate fracture healing, with a focus on clinical applicability in healthy patients without bone disease. The most promising methods identified are the application of axial micromovement, electromagnetic stimulation with electromagnetic fields and direct electric currents, as well as the administration of growth factors and parathyroid hormone. Some interventions have been shown to reduce the healing time by up to 20 to 30%, potentially equivalent to several weeks. As a combination of methods could decrease the healing time even further than one method alone, especially if their mechanisms of action differ, clinical studies in human patients are needed to assess the individual and combined effects on healing progress. Studies are also necessary to determine the ideal settings for the interventions, i.e., optimal frequencies, intensities, and exposure times throughout the separate healing phases. More clinical research is also desirable to create an evidence base for clinical guidelines. To make it easier to conduct these investigations, the development of new methods that allow better quantification of fracture-healing progress and speed in human patients is needed.

Right Ventricular Function and Oxidative Stress Improve with the Administration of Thyroid Hormones and Grape Juice in a Pulmonary Hypertension Model.

Adverse remodeling of lung vessels elevates pulmonary pressure and provokes pulmonary arterial hypertension (PAH). PAH results in increased right ventricle (RV) afterload, causing ventricular hypertrophy and the onset of heart failure. There is no specific treatment for maladaptive RV remodeling secondary to PAH. This study aims to explore two therapeutic approaches, grape juice (GJ) and thyroid hormones (TH), on PAH-induced oxidative stress and cardiac functional changes. Parameters of echocardiography related to lung vessel resistance (AT/ET ratio), RV contractility (TAPSE), and RV diastolic function (E/A peaks ratio) were evaluated. Also, total ROS, lipid peroxidation, antioxidant enzymes, calcium handling proteins, pro-oxidant and antioxidant protein expression were measured. Values of p<0.05 were considered statistically significant. Both GJ and TH treatments demonstrated reductions in pulmonary resistance (~22%) and improvements in TAPSE (inotropism ~11%) and AT/ET ratio (~26%) (p<0.05). There were no changes amongst groups regarding the E/A peak ratio. Although ROS and TBARS were not statistically significant, GJ and TH treatments decreased xanthine oxidase (~49%) levels and normalized HSP70 and calcium handling protein expression (p<0.05). However, only TH treatment ameliorated diastolic function (~50%) and augmented NRF2 immunocontent (~48%) (p<0.05). To the best of our knowledge, this study stands as a pioneer in showing that TH administered together with GJ promoted functional and biochemical improvements in a PAH model. Moreover, our data suggest that GJ and TH treatments were cardioprotective, combined or not, and exhibited their beneficial effects by modulating oxidative stress and calcium-handling proteins.

Regional difference in the distribution of alkaline phosphatase, PHOSPHO1, and calcein labeling in the femoral metaphyseal trabeculae in parathyroid hormone-administered mice

ObjectivesThis study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the murine femora, and whether the PTH-driven bone formation would facilitate osteoblastic differentiation into osteocytes. MethodsSix-week-old male C57BL/6J mice were employed to examine the distribution of alkaline phosphatase (ALP), PHOSPHO1, podoplanin, and calcein labeling in two distinct long bone regions: the metaphyseal trabeculae close to the chondro-osseous junction (COJ) and those distant from the COJ in three mouse groups, a control group receiving a vehicle (sham group) and groups receiving hPTH (1–34) twice a day (PTH BID group) or four times a day (PTH QID group) for two weeks. ResultsThe sham group showed PHOSPHO1-reactive mature osteoblasts localized primarily at the COJ, whereas the PTH BID/QID groups exhibited extended lines of PHOSPHO1-reactive osteoblasts even in regions distant from the COJ. The PTH QID group displayed fragmented calcein labeling in trabeculae close to the COJ, whereas continuous labeling was observed in trabeculae distant from the COJ. Osteoblasts tended to express podoplanin and PHOSPHO1 independently in the close and distant regions of the sham group, while osteoblasts in the PTH-administered groups showed immunoreactivity of podoplanin and PHOSPHO1 together in the close and distant regions. ConclusionsAdministration of PTH may accelerate remodeling-based bone formation in regions close to the COJ while predominantly inducing modeling-based bone formation in distant regions. PTH appeared to simultaneously facilitate osteoblastic bone mineralization and differentiation into osteocytes in both remodeling- and modeling-based bone formation.

GnRH-mediated suppression of S100A4 expression inhibits endometrial epithelial cell proliferation in sheep via GNAI2/MAPK signaling.

Gonadotrophin-releasing hormone (GnRH) administration significantly decreases the pregnancy rate of recipient ewes after embryo transfer, possibly because GnRH affects endometrial epithelial cell function. Therefore, this study investigated the effect of GnRH on endometrial epithelial cells. Transcriptome sequencing was used to determine the regulatory effect of GnRH on the ewe endometrium, and the S100A4 gene, which showed altered transcription, was screened as a candidate regulator of this effect. Endometrial epithelial cells were further isolated, the S100A4 protein was immunoprecipitated, and host proteins that interacted with S100A4 were identified by mass spectrometry. We further verified the effects of S100A4 and GNAI2 on the proliferation of endometrial epithelial cells via overexpression/knockdown experiments and subsequent CCK-8 and EdU assays. The effect of S100A4 deletion in endometrial cells on reproduction was verified in mice with S100A4 knockout. Our results showed that S100A4 gene transcription in endometrial cells was significantly inhibited after GnRH administration. GNAI2 was identified as a downstream interacting protein of S100A4, and S100A4 was confirmed to activate the MAPK signaling pathway to promote cell proliferation by targeting GNAI2. GnRH can suppress the expression of S100A4 in the endometrium, consequently inhibiting the proliferation of endometrial cells through the S100A4/GNAI2/MAPK signaling pathway. These findings suggest a potential explanation for the limited efficacy of GnRH in promoting embryo implantation.

Development and characterization of a novel variant of long-acting bovine follicle-stimulating hormone (brscFSH)

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 μg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8–12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants.

Immunohistochemical and Morphometric Assessment on the Biological Function and Vascular Endothelial Cells in the Initial Process of Cortical Porosity in Mice With PTH Administration.

To clarify the cellular mechanism of cortical porosity induced by intermittent parathyroid hormone (PTH) administration, we examined the femoral cortical bone of mice that received 40 µg/kg/day (four times a day) human PTH (hPTH) (1-34). The PTH-driven cortical porosity initiated from the metaphyseal region and chronologically expanded toward the diaphysis. Alkaline phosphatase (ALP)-positive osteoblasts in the control mice covered the cortical surface, and endomucin-positive blood vessels were distant from these osteoblasts. In PTH-administered mice, endomucin-reactive blood vessels with TRAP-positive penetrated the ALP-positive osteoblast layer, invading the cortical bone. Statistically, the distance between endomucin-positive blood vessels and the cortical bone surface abated after PTH administration. Transmission electron microscopic observation demonstrated that vascular endothelial cells often pass through the flattened osteoblast layer and accompanied osteoclasts in the deep region of the cortical bone. The cell layers covering mature osteoblasts thickened with PTH administration and exhibited ALP, α-smooth muscle actin (αSMA), vascular cell adhesion molecule-1 (VCAM1), and receptor activator of NF-κB ligand (RANKL). Within these cell layers, osteoclasts were found near endomucin-reactive blood vessels. In PTH-administered femora, osteocytes secreted Dkk1, a Wnt inhibitor that affects angiogenesis, and blood vessels exhibited plasmalemma vesicle-associated protein, an angiogenic molecule. In summary, endomucin-positive blood vessels, when accompanied by osteoclasts in the ALP/αSMA/VCAM1/RANKL-reactive osteoblastic cell layers, invade the cortical bone, potentially due to the action of osteocyte-derived molecules such as DKK1.

Biochemical profile and oocyte quality of primiparous Bos indicus cows submitted to a timed artificial insemination protocol

The objective of this study was to verify the causes of the lower response of primiparous Bos indicus cows to the ovulation synchronization protocol. Two experiments were performed to evaluate the biochemical profile, oocyte and follicular cell quality (Experiment 1) and pregnancy (Experiment 2). In Experiment 1, suckled primiparous (n = 24) and multiparous cows (n = 24) were submitted to ovum pick up (OPU). On Day 0 (D0), all cows received 2 mg of estradiol benzoate (EB) and an intravaginal progesterone insert (P4). Five days (D5) after the first hormonal administration (EB + P4), all follicles larger than 3 mm were counted on each ovary, and ovum pick-up (OPU) was performed. On day 12 (D12), the intravaginal progesterone insert was removed, and measurement and aspiration of the largest follicle were performed. Blood samples were collected on D5 and D12 to evaluate the concentrations of glucose, cholesterol, NEFA, IGF-1 and insulin. In Experiment 2, suckled primiparous (n = 50) and multiparous (n = 50) cows were subjected to an ovulation synchronization protocol based on E2/P4 (D0: 2 mg EB plus P4 intravaginal insert; D8: 500 μg of cloprostenol, 1 mg cypionate estradiol and 300UI of eCG; D10: artificial insemination). In addition, blood samples were collected on D10 for evaluation of the same hormones and metabolites described in Experiment 1. In all studies, calves remained with the cows during the experimental period. In experiment 1, the number of oocytes grade 1 (P = 0.83), grade 2 (P = 0.23) and grade 3 (P = 0.51), total number of retrieved oocytes (P = 0.14), oocyte quality index (P = 0.93) and total viable oocytes (P = 0.38) did not differ between primiparous and multiparous cows. The number of follicles at the time of follicular aspiration (20.7 ± 1.5 vs. 18.0 ± 1.9; P = 0.05) and the diameter of the largest follicle on D12 (13.5 ± 0.6 vs. 11.4 ± 0.6; P = 0.04) were greater in multiparous cows, and the number of degenerated oocytes was greater in primiparous cows (1.9 ± 0.7 vs. 1.2 ± 0.3; P = 0.05). On D5, the concentrations of IGF-1 (P = 0.47), insulin (P = 0.08), total cholesterol (P = 0.47), NEFA (P = 0.77) and glucose (P = 0.55) in the blood and IGF-1 (P = 0.97) and insulin (P = 0.11) in the follicular fluid did not differ between parity groups. On D12, there was no difference in the concentrations of IGF-1 (P = 0.26), total cholesterol (P = 0.32), NEFAs (P = 0.31) and glucose (P = 0.93) in the blood between primiparous and multiparous cows, however, the serum insulin concentration (P = 0.04) was higher in primiparous cows. There was no correlation between serum and follicular fluid insulin concentrations (r = 0.17; P = 0.31), however, there was a low correlation between serum and follicular fluid IGF-1 concentrations (r = 0.47; P = 0.002). Quantification of transcripts did not differ between parity groups. In experiment 2, concentrations of NEFA (P = 0.12) and insulin (P = 0.16) in the blood and P/AI (P = 0.93) did not differ between parity [60 % (30/50) primiparous vs. 60 % (30/50) multiparous]. In contrast, blood concentrations of IGF-1 (P = 0.0001), total cholesterol (P = 0.005) and glucose (P = 0.01) were greater in primiparous cows. It was concluded that the oocyte quality and expression of the genes evaluated in the granulosa cells were not different between primiparous and multiparous cows. Unexpectedly, the pregnancy rate did not differ between parity. Nevertheless, the blood concentrations of IGF-1, total cholesterol and glucose were greater in primiparous cows.

Exogenous growth hormone (GH) increases dimension and reduces strength of vertebrae in Atlantic salmon (Salmo salar)

Growth hormone (GH) administration increases bone strength in rats, mainly through alterations of the dimensional proportions of vertebrae. However, similar knowledge is lacking in other clades. In order to pursue this, Atlantic salmon were fed diets with high or low vitamin C and E and administered a slow-release implant of bovine GH.While neither the diets or the GH treatment affected growth, GH reduced condition factor and carcass-somatic index, and increased the hepatosomatic and visceral-somatic indexes. GH had an impact on the dimensional proportions of the vertebrae and increased the relative dorso-ventral and lateral vertebra diameters. Moreover, GH decreased the mechanical strength of the vertebra, both with (modulus of elasticity, failure point) and without (stiffness) normalizing the mechanical data for the dimensions of the vertebrae. Diet did not impact on the vertebra morphometry or mechanical strength. RNA-seq of vertebra centra show that several genes associated with bone growth and remodelling were affected by GH, while there was an interactive effect between diet vitamin level and GH on several genes associated with lipid metabolism.The data may suggest that exogenous GH affects the bone cellular mechanisms of Atlantic salmon postsmolts in such a way that their vertebrae increase in diameter but not length, not disturbing growth in body length. The GH and diet effects on lipid metabolism associated genes indicate a complex regulation of the lipids stored inside the vertebral column by endocrine and nutritional factors.

Can Human Growth Hormone Accelerate Tendon and Ligament Injury Recovery?

Studies involving human fibroblasts and use of human growth hormone (HGH) administration for injury recovery are limited. It is plausible that if the administration of HGH to human cells increased cellular proliferation and differentiation, then HGH might be able to assist in accelerating recovery from injury. HGH will increase proliferation and differentiation of human tendon and ligament fibroblasts in vitro based on both a single-dose and a sustained-dose model of HGH administration. Basic science cellular study. Human tendon and ligament tissue were harvested from 24 patients. Tissue samples were digested with type I collagenase to isolate the target cell types. HGH was administered directly to isolated cells at doses ranging from 100 pg/mL to 10 µg/mL, either in a single-dose or a sustained-dose model. Proliferation was analyzed at days 4 and 7. Differentiation of ligament and tendon fibroblasts was assessed at day 14. Administration of a single-dose of HGH to both cell types demonstrated similar or inferior cellular proliferation compared with controls after 7 days. For the sustained-dosing model of ligament fibroblasts, only the 100 ng/mL concentration demonstrated at least statistically similar or improved proliferation compared with controls. When examining the 100 ng/mL HGH concentration with larger sample sizes, cellular proliferation was not improved over controls for any cell type for the single- or sustained-dosing models. Proliferation for tendon fibroblasts was either similar or inferior to the control group at all concentrations of HGH. There was no clear dose-response relationship demonstrating enhanced collagen production with administration of HGH to suggest it enhances injury recovery. HGH administered to human tendon and ligament fibroblasts does not appear to positively affect cellular proliferation and differentiation. This study does not support the use of HGH for accelerating recovery from injury.

Psoas mass index at the level of the third lumbar vertebra on computed tomography is a prognostic predictor for metastatic castration-sensitive prostate cancer.

Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. The median follow-up was 56.9months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer.

An in vitro validation system for chicken bioreactors using immortalized chicken oviductal epithelial cells

The utilization of chicken oviductal epithelial cells (OECs) as a bioreactor to produce therapeutic proteins has shown promise, but the time taken to obtain transgenic offspring impedes efficient validation of protein production. To overcome this barrier, we focused on the immortalization of chicken OECs (cOECs) using retroviral vector-mediated c-MYC oncogene expression to establish an in vitro pre-validation system for chicken bioreactors. The resulting immortalized cOECs exhibited sustained proliferation, maintained a normal diploid chicken karyotype, and expressed key oviduct-specific genes (OVA, OVM, LYZ, AVD, and ESR1). Notably, hormonal administration of diethylstilbestrol (DES) or progesterone (P4) upregulated oviduct-specific genes in these cells. To enhance the utility of these immortalized cOECs as an in vitro validation system for chicken bioreactors, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology was employed to knock-in (KI) an enhanced green fluorescence protein (EGFP) gene at the ovalbumin (OVA) locus. The resulting OVA EGFP KI immortalized cOECs secreted both EGFP and OVA proteins into the culture medium, with secretion enhanced under DES treatment. This successful integration of an exogenous gene into cOECs enhances their potential as a versatile in vitro validation system for chicken bioreactors. The established immortalized cOECs overcome previous challenges associated with long-term culture and maintenance, providing a reliable platform for efficient protein production validation. This study presents a comprehensive characterization of the immortalized cOECs, addressing critical limitations associated with in vivo systems and laying a foundation for the development of a streamlined and effective chicken bioreactor model.

Effect of Pregnant Mare Serum Gonadotropin and Antidopamine on the gonads of female bileh fish (Rasbora maninjau)

Bileh fish (Rasbora maninjau) still have difficulty spawning in a controlled manner in aquaculture containers because the maturation of female fish gonads is slow and takes a long time. Internal factors, including the hormonal system, strongly influence the maturation of fish gonads. This study aims to determine the effect of Pregnant Mare Serum Gonadotropin (PMSG) and antidopamine on female gonads of bileh fish. The research used an experiment with a CRD (Completely Randomized Design) experimental design. The experiment consisted of four treatments and three repetitions. The treatments were the administration of PMSG and antidopamine hormones at different doses through feed, namely: 0 ml/kg feed (P1), 0.5 ml/kg feed (P2), 1 ml/kg feed (P3) and 2 ml/kg feed (P4). The research procedures included container and fish preparation, hormone, and feed preparation, fish rearing, and data collection. The test parameters evaluated were weight gain (Wg), gonadosomatic index (GSI), and gonadal maturity level (GML). Data on test parameters were analyzed with statistics (Anova). The research results showed that the administration of PMSG hormones and antidopamine through feed had a significant effect on weight gain, gonadosomatic index and gonad maturity level of bileh fish (P<0.05). Effective and best treatment at P3 (1 ml/kg feed) with Wg 0.22grams, GSI 8.58%, and GML IV 60%.

Summary of the 2023 Thai Menopause Society Clinical Practice Guideline on Menopausal Hormone Therapy.

The Thai Menopause Society is an academic organization consisting of healthcare professionals engaged in menopause medicine. The position statement was first issued in 1994 and updated in 2003 and 2023. Herein, we reviewed the important updates of the 2023 position statement on menopausal hormone therapy (MHT) as an international reference for healthcare professionals in Thailand. An advisory panel of clinicians and research experts in the field of menopause reviewed the recommendation of published International Consensus Statements and updated the evidence using the MEDLINE database through PubMed. The evidence-based information and relevant publications were assessed, and a consensus on recommendations was subsequently achieved using the level of evidence to determine the recommendation strength and evidence quality. MHT remains the most effective treatment for vasomotor symptoms and genitourinary syndromes of menopause even after 20 years. Additionally, it is effective in preventing bone loss and fractures in postmenopausal women. The cardiovascular risk of MHT increased in women who initiated MHT after 60 years of age. Hormone therapy should be individualized following the hormone type, dose, administration route, use duration, and progestogen inclusion. The necessary pretreatment evaluation and appropriate follow-up recommendations were added for improved MHT standard care. The updated 2023 Clinical Practice Guideline on MHT is useful for gynecologists, general physicians, endocrinologists, and other healthcare professionals in treating menopausal women receiving hormone therapy in Thailand.

Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the β-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene Bmal1, which was inhibited by NE-βAR signaling. Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.