Influence of nandrolondecanoate on the pituitary-gonadal axis in males

1982 ◽  
Vol 101 (1) ◽  
pp. 108-112 ◽  
Author(s):  
J. W. J. Bijlsma ◽  
S. A. Duursma ◽  
J. H. H. Thijssen ◽  
O. Huber
Keyword(s):  
Rheumatoid Arthritis ◽  
Pilot Study ◽  
Beneficial Effect ◽  
Sex Steroids ◽  
Anabolic Steroids ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Testosterone Secretion ◽  
Lh Secretion

Abstract. Different anabolic steroids can exercise different effects on the pituitary-gonadal axis in males. During a pilot study regarding the possible beneficial effect of the anabolic steroid nandrolondecanoate (ND) on bone metabolism in patients with rheumatoid arthritis additional endocrinological parameters were studied. A significant decrease was found in the serum levels of testosterone, androstenedione and FSH and the ratio of testosterone/oestradiol. There was a significant increase in the serum levels of oestrone. The levels of oestradiol, SHBG, LH and cortisol remained unchanged. An inhibitory effect of ND on testicular testosterone secretion is assumed. The decrease in androstenedione levels is explained by the diminished testosterone secretion. The rise in oestrone levels is explained by peripheral aromatizing of ND to oestrogens. The presented findings are in accordance with the hypothesis that sex steroids can act directly on the pituitary resulting in selective FSH and LH secretion. The possible role of the ratio testosterone/oestradiol in controlling gonadotrophin output is discussed.

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

scholarly journals Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2453-2463 ◽  
Author(s):  
Silvia León ◽  
Chrysanthi Fergani ◽  
Rajae Talbi ◽  
Serap Simavli ◽  
Caroline A Maguire ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Neurokinin A ◽  
Central Control ◽  
Gnrh Release ◽  
Lh Release ◽  
Timing Of Puberty ◽  
Puberty Onset ◽  
Lh Secretion

Abstract The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release.

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

2019 ◽  
Vol 64 (11) ◽  
pp. 673-676
Author(s):  
Asmaya Saftar Huseynova
Keyword(s):  
Rheumatoid Arthritis ◽  
Parathyroid Hormone ◽  
Bone Loss ◽  
Hypovitaminosis D ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
High Production ◽  
Serological Variant

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

scholarly journals The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Samuel García ◽  
Carmen Conde
Keyword(s):  
Rheumatoid Arthritis ◽  
Septic Shock ◽  
Dna Repair ◽  
Beneficial Effect ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Genomic Stability ◽  
Inflammatory Processes ◽  
Parp 1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

Relation of the Serum Levels of DKK-1 and Osteoprotegerin with Bone Mass in Tightly Controlled Rheumatoid Arthritis.

2020 ◽  
Vol 16 ◽  
Author(s):  
Carmen Gómez-Vaquero ◽  
Irene Martín ◽  
Andrea Zacarías ◽  
Pedro Alía ◽  
Estíbaliz Loza ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lumbar Spine ◽  
Femoral Neck ◽  
Serum Levels ◽  
Mineral Density ◽  
Annual Percent Change ◽  
Activity Measures ◽  
Mean Time

Objective: To analyze the association between serum levels of osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and the annual percent change (%) in bone mineral density (BMD) in patients with tightly controlled rheumatoid arthritis (RA). Methods: Observational mixed-study. RA patients followed-up with a tight-control strategy were included. Bone densitometries were performed at baseline (T0) and follow-up (T1) and serum levels of OPG and DKK-1 were measured by ELISA also in T0 and T1; additional clinical variables included disease activity measures, and treatment for RA and osteoporosis. Descriptive bivariate and multivariate analyses, stratified by gender, were performed. Results: We included 97 RA patients (70% female, with a mean age of 53 years, and 76% with low activity by DAS28); 95% were treated with DMARDs and 37% with anti-osteoporotic drugs. Mean time between T0 and T1 was 2.7 years. Most patients had their BMD improved. The mean %BMD was +0.42% for lumbar spine, +0.15% for femoral neck and +0.91% for total femur. In men, baseline OPG was significantly associated with higher BMD loss (β coefficient -0.64) at femoral neck. In women, DKK-1 was associated with higher BMD loss at femoral neck (β coefficient -0.09), and total femur (β coefficient -0.11); however, DKK-1 was associated with lower BMD loss at lumbar spine (β coefficient 0.06). Conclusion: In tightly controlled RA patients, we have found no evidence of bone loss. The role of DKK1 and OPG seems small and might be related to sex and to location.

Circulating Leptin and Adiponectin Concentrations During Tumor Necrosis Factor Blockade in Patients with Active Rheumatoid Arthritis

2009 ◽  
Vol 36 (4) ◽  
pp. 724-730 ◽  
Author(s):  
CALIN POPA ◽  
MIHAI G. NETEA ◽  
JACQUELINE de GRAAF ◽  
FRANK H.J. van den HOOGEN ◽  
TIMOTHY R.D.J. RADSTAKE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Tumor Necrosis ◽  
Active Rheumatoid Arthritis ◽  
Disease Activity Score ◽  
Serum Levels ◽  
Plasma Leptin ◽  
Necrosis Factor

Objective.Adipocytokines, including leptin and adiponectin, may play an important role in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of longterm therapeutic tumor necrosis factor (TNF) blockade on adipocytokine concentrations in patients with RA.Methods.We studied 58 RA patients starting anti-TNF therapy and 58 healthy controls matched for age, sex, and body mass index (BMI). Fasting blood samples were drawn at baseline, 2 weeks, and 6 months after the start of anti-TNF therapy and serum levels of leptin and adiponectin were measured.Results.Patients with RA had increased adiponectin (p < 0.001) and similar leptin concentrations compared with the controls. Leptin concentrations were significantly higher in patients with high BMI (p < 0.001) and correlated positively with BMI at all timepoints (r > 0.75). In contrast, serum adiponectin tended to be higher in lean RA patients and did not correlate with BMI at any timepoint. There were no clear correlations between serum concentrations of adipocytokines and disease activity (Disease Activity Score 28). Short or longterm TNF blockade alone had no influence on circulating leptin and adiponectin concentrations. Patients treated with anti-TNF and concomitant corticosteroids on a stable basis showed a significant decrease in adiponectin levels after 6 months of therapy (p < 0.025).Conclusion.In patients with RA, chronic inflammation and its suppression during anti-TNF therapy have limited influence on plasma leptin concentrations, while significantly decreasing circulating adiponectin levels. Our findings question the suggested key role of inflammatory markers in regulating adipocytokine patterns in RA.

scholarly journals The role of IL-18 in addition to Th17 cytokines in rheumatoid arthritis development and treatment in women

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgi Vasilev ◽  
Irena Manolova ◽  
Mariana Ivanova ◽  
Iskren Stanilov ◽  
Lyuba Miteva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Duration ◽  
Early Stage ◽  
Serum Levels ◽  
Treatment Regimens ◽  
Rheumatoid Arthritis Development ◽  
Tnf Α ◽  
Th17 Cytokines ◽  
Pro Inflammatory Cytokines

AbstractWe aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04–175.3] vs 4.64 pg/ml [2.95–13.31], p = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients’ subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients.

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