Circulating miR-30b levels increase during male puberty

2021 ◽  
Author(s):  
Tero Varimo ◽  
Yafei Wang ◽  
Päivi J. Miettinen ◽  
Kirsi Vaaralahti ◽  
Matti Hero ◽  
...  
Keyword(s):  
Aromatase Inhibitor ◽  
Low Dose ◽  
Inhibin B ◽  
Testicular Volume ◽  
Hpg Axis ◽  
Relative Expression ◽  
Male Puberty ◽  
Constitutional Delay ◽  
Design And Methods

OBJECTIVE: The role of microRNAs as endocrine regulators is emerging, and microRNA mir-30b has been reported to repress Mkrn3. However, the expression of miR-30b during male puberty has not been studied. DESIGN AND METHODS: Circulating relative miR-30b expression was assessed in sera of 26 boys with constitutional delay of growth and puberty (CDGP), treated with low-dose testosterone (T) (n=11) or aromatase inhibitor letrozole (n=15) for 6 months and followed up to 12 months (NCT01797718). The associations between the relative expression of miR-30b and hormonal markers of puberty were evaluated. RESULTS: During the 12 months of the study, circulating miR-30b expression increased 2.4 ± 2.5 (SD) fold (p=0.008) in all boys, but this change did not correlate with corresponding changes in LH, testosterone, inhibin B, FSH, or testicular volume (p=0.25-0.96). Lz-induced activation of the hypothalamic-pituitary-gonadal (HPG) axis was associated with more variable miR-30b responses at 3 months (P<0.05), whereas those treated with T exhibited significant changes in relative miR-30b levels in the course the study (p<0.01-0.05). CONCLUSIONS: Circulating miR-30b expression in boys with CDGP increases in the course of puberty, and appears to be related to the activity of the HPG axis.

Management of Puberty in Constitutional Delay of Growth and Puberty

2001 ◽  
Vol 14 (s2) ◽  
Author(s):  
F. De Luca ◽  
J. Argente ◽  
L. Cavallo ◽  
E. Crowne ◽  
H.A. Delemarre-Van de Waal ◽  
...  
Keyword(s):  
Social Relationships ◽  
School Performance ◽  
Low Dose ◽  
Well Being ◽  
Growth Potential ◽  
Sex Steroid ◽  
Optimal Timing ◽  
Short Course ◽  
Constitutional Delay

AbstractConstitutional delay of growth and puberty (CDGP) is the most common presenting form of short stature, but no single test can infallibly discriminate CDGP and isolated hypogonado- trophic hypogonadism. Management of puberty in CDGP aims to optimise not only growth - maintaining body proportions and improving peak bone mass without impairing growth potential - but also well-being; for example, the distress boys often suffer because of their lack of growth and pubertal progression can affect their school performance and social relationships. Typical sex steroid treatments to induce puberty in boys with CDGP include testosterone (T) enanthate, T undecanoate, mixed T esters, T transdermal patches, and oxandrolone p.o. Compared with other regimens, short-course low-dose depot T i.m. is an effective, practical, safe, well tolerated, and inexpensive regimen. Some unresolved problems in management include optimal timing and dose of sex steroid treatment, the role of GH in CDGP, and the management of CDGP in girls.

scholarly journals Role of percutaneous testis biopsy in management of patients with azoospermia

2020 ◽  
Vol 7 (3) ◽  
pp. 43-50
Author(s):  
N. G. Gasanov ◽  
S. I. Gamidov ◽  
T. V. Shatylko ◽  
A. Yu. Popova ◽  
N. P. Makarova ◽  
...  
Keyword(s):  
Testicular Biopsy ◽  
Inhibin B ◽  
Testicular Volume ◽  
Thermal Mode ◽  
Limited Effectiveness ◽  
Puncture Biopsy ◽  
History Of ◽  
Production Frequency ◽  
Immediate Transition

Purpose of the study. To determine the practical value of puncture methods for obtaining spermatozoa in azoospermia. Patients and methods. The results of 127 puncture biopsies of testis (TESA) and testicular appendage (PESA) in patients with azoospermia of presumably obstructive origin were analyzed. The sperm production frequency (SPF) was calculated, as well as the frequency of transition to an open testicular biopsy. Was built a logistic regression model to analyze factors influencing the result, TESA / PESA, which included as independent variables the following parameters: patient age, duration of involuntary infertility, the level of sex hormones (testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, progesterone, inhibin B), the total volume of testes, presence of varicocele, the presence of chemotherapy or radiation therapy, a history of alcohol abuse, Smoking, regular violation of the thermal mode, surgery in the inguinal and scrotal region. Indicators of the probability ratio (PR) with a 95% confidence interval (95% CI) were obtained. Results. 92 biopsy attempts out of 127 were successful, and the NPV was 72.4%. Independent statistically significant predictors of PESA / TESA success were testicular volume (PR = 1.113; 95% CI = 1.026–1.207) and inhibin b level (PR = 1.026; 95% CI = 1.011–1.041). In 35 patients whose spermatozoa were not found during the puncture biopsy, conversion to open microsurgical biopsy was performed. Conclusion. PESA and TESA have only limited effectiveness in azoospermia. We believe that puncture biopsy of the testicles and epididymis is justified only in patients with normal testicular volume and high levels of inhibin B. PESA / TESA should be performed in conditions that allow immediate transition to an open biopsy in case of failure.

scholarly journals Serum inhibin B for differentiating between congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty: a systematic review and meta-analysis

Endocrine ◽  
2021 ◽  
Author(s):  
Yuting Gao ◽  
Qin Du ◽  
Liyi Liu ◽  
Zhihong Liao
Keyword(s):  
Systematic Review ◽  
Study Design ◽  
Meta Analysis ◽  
Hypogonadotropic Hypogonadism ◽  
Inhibin B ◽  
Testicular Volume ◽  
Assay Method ◽  
Cochrane Library ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Constitutional Delay

Abstract Purpose The distinction between congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) in patients with delayed puberty is difficult to distinguish, but important for timely treatment. The aim of this study is to perform a systematic review and meta-analysis to determine the diagnostic performance of serum inhibin B (INHB) levels for differentiating CHH and CDGP. Methods PubMed, EMBASE, and Cochrane Library databases were systematically searched from the date of database inception to November 10, 2019 for studies examining the use of serum INHB to discriminate between CHH and CDGP. Pooled odds ratios (OR), sensitivity, specificity, and 95% confidence intervals (CI) were calculated. The Quality Assessment of Diagnostic Studies-2 (QUADAS-2) was used to assess the quality of the included studies. Sub-analyses were performed including that based on testicular volume (TV) and study design. Results Seven studies, comprising of 349 patients (96 CHH and 253 CDGP), were included in the meta-analysis. For differentiating between CHH and CDGP, INHB level exhibited good diagnostic accuracy with a pooled sensitivity of 92% (95% confidence interval [CI]: 0.86–0.96, I2 = 0.4%, p = 0.4343), specificity of 92% (95% CI: 0.88–0.94, I2 = 68.1%, p = 0.0009), and pooled area under the receiver operating characteristic curve (AUC) of 0.9619. The cut-off values of INHB for boys were 56, 66, 80, 96, 94.7, 111, and 113 pg/ml (assay method standardized to Gen II ELISA). Sub-analyses showed that testicular volume and study design could be a source of statistically significant heterogeneity in specificity. In boys with a testicular volume of ≤3 ml, INHB performed well with a sensitivity of 92%, specificity of 98%, and AUC of 0.9956. Conclusion INHB exhibits excellent diagnostic efficiency in distinguishing CHH from CDGP, especially in boys with severe puberty deficiency (TV ≤ 3 ml).

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

Reactive oxygen species in cell responses to toxic agents

2002 ◽  
Vol 21 (2) ◽  
pp. 85-90 ◽  
Author(s):  
L E Feinendegen
Keyword(s):  
Radiation Exposure ◽  
Mammalian Cells ◽  
Low Dose ◽  
X Rays ◽  
Low Dose Radiation ◽  
Cell Responses ◽  
Toxic Agents ◽  
Particle Tracks ◽  
Dose Radiation

This review first summarizes experimental data on biological effects of different concentrations of ROS in mammalian cells and on their potential role in modifying cell responses to toxic agents. It then attempts to link the role of steadily produced metabolic ROS at various concentrations in mammalian cells to that of environmentally derived ROS bursts from exposure to ionizing radiation. The ROS from both sources are known to both cause biological damage and change cellular signaling, depending on their concentration at a given time. At low concentrations signaling effects of ROS appear to protect cellular survival and dominate over damage, and the reverse occurs at high ROS concentrations. Background radiation generates suprabasal ROS bursts along charged particle tracks several times a year in each nanogram of tissue, i.e., average mass of a mammalian cell. For instance, a burst of about 200 ROS occurs within less than a microsecond from low-LET irradiation such as X-rays along the track of a Compton electron (about 6 keV, ranging about 1 μm). One such track per nanogram tissue gives about 1 mGy to this mass. The number of instantaneous ROS per burst along the track of a 4-meV ¬-particle in 1 ng tissue reaches some 70000. The sizes, types and sites of these bursts, and the time intervals between them directly in and around cells appear essential for understanding low-dose and low dose-rate effects on top of effects from endogenous ROS. At background and low-dose radiation exposure, a major role of ROS bursts along particle tracks focuses on ROS-induced apoptosis of damage-carrying cells, and also on prevention and removal of DNA damage from endogenous sources by way of temporarily protective, i.e., adaptive, cellular responses. A conclusion is to consider low-dose radiation exposure as a provider of physiological mechanisms for tissue homoeostasis.

scholarly journals Larger Testes and Higher Inhibin B Levels in Finnish than in Danish Newborn Boys

2006 ◽  
Vol 91 (7) ◽  
pp. 2732-2737 ◽  
Author(s):  
Katharina M. Main ◽  
Jorma Toppari ◽  
Anne-Maarit Suomi ◽  
Marko Kaleva ◽  
Marla Chellakooty ◽  
...  
Keyword(s):  
Sperm Quality ◽  
Genetic Difference ◽  
Reproductive Hormones ◽  
Inhibin B ◽  
Testicular Volume ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Testis Size ◽  
University Hospitals ◽  
Prospective Longitudinal

Abstract Context: Recent studies showed that male reproductive health problems, such as cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more prevalent in Denmark than in Finland. Objectives: We hypothesized that, if fetal testicular dysgenesis contributed to these observations, differences in gonadal development and the hypothalamus-pituitary-testis axis would already be detectable perinatally. Thus, we investigated healthy newborn boys in both countries. Design: This was a prospective, longitudinal population-based study. Setting: Two primary obstetric centers were included at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. Participants: The participants of the study included 633 Danish and 1044 Finnish boys, born at term with appropriate weight for gestational age. Interventions: Ultrasound determination of testis size at 0, 3, and 18 months and blood sampling (n = 727) at 3 months were analyzed. Main Outcome Measures: Testicular volume and reproductive hormones were measured. Results: Testis volume was significantly higher at all ages in Finnish than in Danish boys (medians, 98 vs. 95, 185 vs. 119, and 188 vs. 136 mm3, respectively; P &lt; 0.00001). Testis growth from birth to 3 months was larger in Finnish than in Danish boys (mean, 75 vs. 26 mm3; P &lt; 0.0001). Serum hormone levels were higher in Finnish than Danish boys for inhibin B (median, 456 vs. 385 pg/ml; P &lt; 0.0001), FSH (1.33 vs. 1.21 IU/liter; P &lt; 0.036), and SHBG (143 vs. 136 nmol/liter; P &lt; 0.022). Inhibin B was significantly positively correlated to testicular volume (r = 0.25; P &lt; 0.006). Conclusions: The larger testes and higher inhibin B levels most likely represent a bigger volume of seminiferous tubules in Finnish compared with Danish boys. Although this phenomenon may be attributable to a genetic difference between the two countries, it may also reflect environmental factors influencing testicular development.

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