scholarly journals Serum levels of insulin-like factor 3, anti-Müllerian hormone, inhibin B, and testosterone during pubertal transition in healthy boys: a longitudinal pilot study

Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 529-535 ◽  
Author(s):  
Marie Lindhardt Johansen ◽  
Ravinder Anand-Ivell ◽  
Annette Mouritsen ◽  
Casper P Hagen ◽  
Mikkel G Mieritz ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Cell Function ◽  
Serum Levels ◽  
Reproductive Hormones ◽  
Inhibin B ◽  
Testicular Volume ◽  
Serum Concentrations ◽  
Pubertal Onset ◽  
Additional Information ◽  
And Function

Insulin-like factor 3 (INSL3) is a promising marker of Leydig cell function with potentially high clinical relevance. Limited data of INSL3 levels in relation to other reproductive hormones in healthy pubertal boys exist. In this study, we aimed to evaluate longitudinal serum changes in INSL3 compared with LH, FSH, testosterone, inhibin B, and anti-Müllerian hormone (AMH) during puberty in healthy boys. Ten boys were included from the longitudinal part of the COPENHAGEN Puberty Study. Pubertal evaluation, including testicular volume, was performed and blood samples were drawn every 6 months for 5 years. Serum concentrations of testosterone were determined by a newly developed LC–MS/MS method, and serum concentrations of INSL3, AMH, inhibin B, FSH, and LH respectively were determined by validated immunoassays. The results showed that serum INSL3 levels increased progressively with increasing age, pubertal onset, and testicular volume. In six of the ten boys, LH increased before the first observed increase in INSL3. In the remaining four boys, the increase in LH and INSL3 was observed at the same examination. The increases in serum concentrations of LH, testosterone, and INSL3 were not parallel or in ordered succession and varied interindividually. We demonstrated that INSL3 concentrations were tightly associated with pubertal onset and increasing testicular volume. However, the pubertal increases in LH, INSL3, and testosterone concentrations were not entirely parallel, suggesting that INSL3 and testosterone may be regulated differently. Thus, we speculate that INSL3 provides additional information on Leydig cell differentiation and function during puberty compared with traditional markers of testicular function.

scholarly journals Compensatory function of the remaining testis is dissociated in boys and adolescents with monorchidism

2016 ◽  
Vol 174 (3) ◽  
pp. 399-407 ◽  
Author(s):  
Romina P Grinspon ◽  
Carolina Habib ◽  
Patricia Bedecarrás ◽  
Silvia Gottlieb ◽  
Rodolfo A Rey
Keyword(s):  
Leydig Cells ◽  
Cell Function ◽  
Serum Testosterone ◽  
Compensatory Hypertrophy ◽  
Reproductive Hormones ◽  
Testicular Volume ◽  
Healthy Controls ◽  
Cross Sectional ◽  
And Function ◽  
Circulating Levels

ObjectiveCompensatory hypertrophy has been classically described in patients with monorchidism. However, it remains unclear whether there is a functional compensatory activity of the different cell populations. Our aim was to assess the functional capacity of the solitary testis in monorchid males from infancy through puberty in order to determine whether the remaining gonad is capable of compensating the functional activity of Sertoli and Leydig cells of the absent gonad.DesignIn a retrospective, cross-sectional, analytical study performed at a tertiary paediatric public hospital, we included 89 boys with monorchidism and 358 healthy controls, aged 6 months–18 years. Testicular volume and circulating levels of reproductive hormones were compared between patients with monorchidism and normal boys. Serum anti-Müllerian hormone (AMH) and FSH were used as biomarkers of the functional mass of prepubertal Sertoli cells, whereas serum testosterone and LH were used as biomarkers of Leydig cells.ResultsIn the vast majority of the cases, the testicular volume of monorchid boys was smaller than the sum of the volume of both testes of healthy controls. Serum AMH was lower and FSH was higher in patients with monorchidism than in controls aged <3 and >13 years. Serum testosterone and LH did not differ significantly between patients and controls.ConclusionIn boys and adolescents with monorchidism, there is a dissociated capacity of the remaining testis to compensate for the absence of the other gonad: while Leydig cell function is largely compensated, Sertoli cell proliferation and function was lower than in controls.

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.

scholarly journals Assessment of Propolis Supplementation on Serum Concentrations of Liver Enzymes in Endurance Athletes with Four Weeks Aerobic Training

2021 ◽  
Vol 25 (1) ◽  
pp. 25-30
Author(s):  
Mojtaba Mahdavi Asiabar ◽  
◽  
Mokhtar Nasiri Farsani ◽  
Nematollah Gheibi ◽  
◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Aerobic Training ◽  
Liver Enzymes ◽  
Cell Function ◽  
Serum Levels ◽  
Exercise Group ◽  
Cellular Level ◽  
Endurance Athletes ◽  
Serum Concentrations ◽  
Significant Difference

Background: Aerobic and intense exercises with an increase in free radicals cause damages at the cellular level, heart disease, cancer, and the development of aging processes, which one of its symptoms is increased serum concentrations of liver enzymes. Objective: The purpose of this study was to investigate the concurrent effect of four weeks of aerobic training and propolis supplementation on the activity of liver enzymes, including ALT, AST, and SOD in endurance athletes. Methods: Thirty-two male athletes (age: 21±1.4 years) in track and field were randomly divided into three groups: exercise group, exercise with placebo group, and exercise with supplement group. Propolis supplementation was taken as two tablets (500 mg) twice a day and aerobic exercise was performed for 4 weeks and in 24 sessions with an intensity of 60 to 65% of heart rate. The statistical method was done using one-way ANOVA and Tukey post hoc test by SPSS v. 18 software. Findings: The results showed that there was a statistically significant difference between groups in serum levels of SOD, AST, and ALT (P<0.05). There was not a statistically significant difference between the exercise group and placebo+exercise group in serum levels of SOD, AST, and ALT (P>0.05). Conclusion: The results showed that aerobic exercise alone can increase SOD levels and propolis supplementation with aerobic exercise can reduce AST and ALT serum levels and lead to improved liver cell function.

scholarly journals Serum inhibin B, FSH, LH and testosterone levels before and after human chorionic gonadotropin stimulation in prepubertal boys with cryptorchidism

2002 ◽  
Vol 147 (1) ◽  
pp. 95-101 ◽  
Author(s):  
P Christiansen ◽  
AM Andersson ◽  
NE Skakkebaek ◽  
A Juul
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Sertoli Cells ◽  
Cell Function ◽  
Serum Levels ◽  
Inhibin B ◽  
Seminiferous Tubules ◽  
Bilateral Cryptorchidism ◽  
Prepubertal Boys ◽  
Baseline Levels

BACKGROUND: Several studies have indicated that cryptorchidism is associated with degenerative changes in both Sertoli cells and germ cells. The gonadal peptide hormone inhibin B reflects Sertoli cell function. Low inhibin B levels are found in a large portion of formerly cryptorchid men who show compromised seminiferous tubule function. It is not known if inhibin B can be used to demonstrate early damage of seminiferous tubules in prepubertal boys with cryptorchidism. METHODS: We investigated the relationship between serum levels of inhibin B, testosterone, FSH and LH in 62 prepubertal boys with uni- and bilateral cryptorchidism. Furthermore, we investigated the changes in serum levels of inhibin B and the corresponding changes in serum levels of FSH, LH and testosterone during a short course (3 weeks) of human chorionic gonadotropin (hCG) injections in 18 of these cryptorchid boys. RESULTS: In the 62 prepubertal boys with uni- or bilateral cryptorchidism there were no significant differences in baseline levels (median and range) of inhibin B (88 (20-195) pg/ml vs 78 (35-182) pg/ml; not significant), LH (0.08 (<0.05-0.99) IU/l vs 0.06 (<0.05-1.61) IU/l; not significant) and FSH (0.60 (0.08-3.73) IU/l vs 0.85 (0.25-2.55); not significant) compared with 156 healthy prepubertal boys, and there were no differences in hormonal levels between boys with uni- or bilateral cryptorchidism. There was no correlation between baseline levels of inhibin B and FSH. In boys younger than 9 years, we found no correlation between baseline levels of inhibin B and LH whereas, in boys older than 9 years, baseline levels of inhibin B were positively correlated to baseline LH (Spearman rank correlation coefficient ((R(s))=0.58, P=0.03). Treatment with hCG (1500 IU intramuscularly twice weekly for 3 weeks) resulted in descensus of testes in 9 out of 18 patients. In all boys but one, irrespective of age, hCG induced a marked increase in testosterone into the adult range (from undetectable to 21.8 (7.0-35.4) nmol/l; P<0.001) and completely suppressed FSH and LH levels. Serum levels of inhibin B increased significantly from 116 (50-195) pg/ml to 147 (94-248) pg/ml (P<0.05), but not uniformly. The increase in serum levels of inhibin B was inversely correlated to baseline inhibin B (Rs=-0.52, P=0.03) and baseline FSH (R(s)=-0.59, P<0.01). CONCLUSIONS: We therefore suggest that, in the prepubertal testes, inhibin B is secreted from the prepubertal Sertoli cells following hCG, whereas early pubertal testes with more differentiated Sertoli cells are not able to secrete inhibin B in response to hCG stimulation, perhaps due to lack of germ cell-derived betaB-subunits. We found (a) normal inhibin B levels in prepubertal boys with uni- or bilateral cryptorchidism, (b) that hCG stimulated testosterone markedly and suppressed FSH and LH levels and (c) that hCG treatment stimulated inhibin B levels in the youngest cryptorchid boys. In the oldest prepubertal boys no hCG-induced changes in inhibin B were shown.

scholarly journals Distinguishing between hidden testes and anorchia: the role of endocrine evaluation in infancy and childhood

2020 ◽  
Vol 183 (1) ◽  
pp. 107-117 ◽  
Author(s):  
Kirstine Jespersen ◽  
Marie Lindhardt Ljubicic ◽  
Trine Holm Johannsen ◽  
Peter Christiansen ◽  
Niels E Skakkebaek ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Testicular Tissue ◽  
Diagnostic Value ◽  
Reproductive Hormones ◽  
Inhibin B ◽  
Control Group ◽  
Serum Concentrations ◽  
Diagnostic Challenge ◽  
Bilateral Cryptorchidism ◽  
Wide Range

Objective Non-palpable testes remain a diagnostic challenge, often involving exploratory laparoscopy. We evaluated the diagnostic value of a wide range of reproductive hormones in order to distinguish between bilateral cryptorchidism and bilateral anorchia. Design In this retrospective study, we identified and included 36 boys with non-palpable testes (20 with cryptorchidism, 3 with congenital hypogonadotropic hypogonadism (CHH), and 13 with anorchia) at first examination during childhood. Methods Information on karyotype, phenotype, surgical results from laparoscopy, and biochemistry was retrieved from patient files. We compared serum concentrations of AMH, inhibin B, FSH, LH, testosterone, estradiol, and hCG stimulation testing in cryptorchid and anorchid boys to serum concentrations in a large, age-matched control group. Receiver-operating characteristic curves were used to determine the cut-off values of each reproductive hormone as a predictor of the presence of functional testicular tissue. Results Concentrations of AMH in 0–1 year olds: ≥155 pmol/L and >1–15 year olds: ≥19 pmol/L, inhibin B (≥22 pg/mL and ≥4 pg/mL), FSH (≤28.9 IU/L and ≤20.3 IU/L) and hCG-induced testosterone (>1-15 year olds: ≥2 nmol/L) were significantly sensitive and specific markers in predicting the presence of functional testicular tissue in boys with non-palpable testes. In infancy, anorchid infants had significantly elevated gonadotropin levels, while CHH had low levels. Conclusion Our findings suggest that laparoscopy may not be necessary in all boys with non-palpable testes if reproductive hormones unequivocally confirm the presence of functional testicular tissue. However, proving the absence may still be a diagnostic challenge.

Altered Leydig cell function in patients with testicular cancer: evidence for a bilateral testicular defect

1983 ◽  
Vol 102 (4) ◽  
pp. 616-624 ◽  
Author(s):  
P. H. B. Willemse ◽  
D. Th. Sleijfer ◽  
W. J. Sluiter ◽  
H. Schraffordt Koops ◽  
H. Doorenbos
Keyword(s):  
Testicular Cancer ◽  
Leydig Cell ◽  
Cell Function ◽  
Serum Levels ◽  
Group Iii ◽  
Testosterone Levels ◽  
Group I ◽  
Testicular Carcinoma ◽  
Group Ii ◽  
Leydig Cell Function

Abstract. In search of an abnormality in Leydig cell function in patients with testicular cancer, serum levels of testosterone, oestradiol, LH and FSH were compared in 3 groups of men. Group I comprised 26 patients studied after recent orchidectomy for a testicular carcinoma, group II 8 patients operated for benign testicular lesions and group III 8 normal controls. In group II normal testosterone values were found as a result of increased LH release. In group I patients, however, testosterone levels often were low, despite elevated LH levels and increased LH capacity. Evidently, in these patients a partial Leydig cell insufficiency may be present, which does not recover within one year of orchidectomy. After removal of one testis for benign disease, normal testosterone levels are maintained by increased LH levels. After orchidectomy for testicular carcinoma a partial Leydig cell insufficiency may be revealed, which seems to have a permanent character. A pre-existent Leydig cell insufficiency of the remaining testis in patients with testicular cancer indicates a bilateral testicular defect.

Changes in the bioactivity to immunoreactivity ratio of circulating luteinizing hormone in impotent men treated with testosterone undecanoate

1989 ◽  
Vol 120 (3) ◽  
pp. 284-288 ◽  
Author(s):  
C. Carani ◽  
M. F. Celani ◽  
D. Zini ◽  
A. Baldini ◽  
L. Della Casa ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Serum Levels ◽  
Mean Value ◽  
Serum Concentrations ◽  
Placebo Administration ◽  
In Vitro Bioassay ◽  
Testosterone Undecanoate ◽  
The Mean ◽  
Mouse Leydig Cell

Abstract. Testosterone undecanoate was administered orally (80 mg twice daily) for 30 days to 10 impotent men with mild Leydig cell failure, age 28 to 42 years. Placebo was administered for 30 days both before and at the end of testosterone undecanoate therapy. Serum levels of bioactive LH, immunoreactive LH and testosterone were determined in basal conditions (day zero), 30 days after the first placebo administration, at the 15th and 30th day of testosterone undecanoate therapy, and at the end of the second treatment with placebo (90th day). Bioactive LH was measured by a sensitive and specific in vitro bioassay based on testosterone production by mechanically dispersed mouse Leydig cell preparations. Immunoreactive LH and testosterone were determined by a doubleantibody RIA technique. The results were compared with those obtained in 30 untreated normal young men. In the basal state, serum concentrations of immunoreactive LH were significantly higher in the patients (P< 0.02) than in control subjects, whereas testosterone levels were significantly lower (P< 0.001) in the impotent men. In contrast, bioactive LH levels and the bioactive LH to immunoreactive LH ratios were similar in the two groups. In the patients, at the 15th day of treatment with testosterone undecanoate, serum levels of testosterone and bioactive LH were significantly higher (P< 0.01) than basal values, whereas immunoreactive LH concentrations showed no significant changes. Consequently, the bioactive LH to immunoreactive LH ratios rose significantly (P< 0.01). At the 30th day of treatment with testosterone undecanoate, the mean value of bioactive LH and the mean bioactive LH to immunoreactive LH ratio were significantly higher (P< 0.01) in the patients than in control men, whereas the mean levels of testosterone and immunoreactive LH were similar in the two groups. Neither the first nor the second treatment with placebo changed the hormone values observed in basal conditions. The results support the experimental evidence that androgens may increase the bioactivity of circulating LH.

scholarly journals Serum levels of inhibin B in adolescents after varicocelelectomy: A long term follow up

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 204-206 ◽  
Author(s):  
Francesco Molinaro ◽  
Elisa Cerchia ◽  
Alfredo Garzi ◽  
Francesco Maria Severi ◽  
Rossella Angotti ◽  
...  
Keyword(s):  
Linear Regression Analysis ◽  
Serum Levels ◽  
Inhibin B ◽  
Surgical Correction ◽  
Testicular Volume ◽  
Paediatric Surgery ◽  
Positive Correlation ◽  
Adolescent Patients ◽  
T1 And T2 ◽  
The Impact

AbstractIntroductionTo study the impact on adult’s fertility of serum inhibin B levels in adolescent patients with idiopathic varicocele after minimally invasive surgical correction and to compare fluctuation of pituitary-testis hormonal values and testicular volumes. Materials and Methods: A case-control study was carried out on a group adolescent patients (n=60) affected by idiopathic left varicocele (group V) and compared with control adolescents (n=40) in the Paediatric Surgery Section of Siena (from June 1993 till September 2013). Inhibin B levels and testicular volume before (T0) and after at 6 and 12 months from surgery (T1 and T2) were evaluated. Results: A positive correlation between testicular growth at T1 and T2 (P<0.001) was found. Linear regression analysis showed a positive correlation between inhibin B levels and testicular volume (expressed as the sum of the right and left values) (P<0.0001). Conclusions: Inhibin B levels are a valid marker for studying the effects of varicocele on the testicular function and confirm the necessity of early surgical correction for preventing the trophic testicular damage and male infertility.

scholarly journals GATA4 Is a Key Regulator of Steroidogenesis and Glycolysis in Mouse Leydig Cells

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1860-1872 ◽  
Author(s):  
Anja Schrade ◽  
Antti Kyrönlahti ◽  
Oyediran Akinrinade ◽  
Marjut Pihlajoki ◽  
Merja Häkkinen ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Metabolic Regulation ◽  
Cell Function ◽  
Primary Cultures ◽  
Tumor Cell Line ◽  
Targeted Mutagenesis ◽  
Spectrometric Analysis ◽  
And Function

Transcription factor GATA4 is expressed in somatic cells of the mammalian testis. Gene targeting studies in mice have shown that GATA4 is essential for proper differentiation and function of Sertoli cells. The role of GATA4 in Leydig cell development, however, remains controversial, because targeted mutagenesis experiments in mice have not shown a consistent phenotype, possibly due to context-dependent effects or compensatory responses. We therefore undertook a reductionist approach to study the function of GATA4 in Leydig cells. Using microarray analysis and quantitative RT-PCR, we identified a set of genes that are down-regulated or up-regulated after small interfering RNA (siRNA)-mediated silencing of Gata4 in the murine Leydig tumor cell line mLTC-1. These same genes were dysregulated when primary cultures of Gata4flox/flox adult Leydig cells were subjected to adenovirus-mediated cre-lox recombination in vitro. Among the down-regulated genes were enzymes of the androgen biosynthetic pathway (Cyp11a1, Hsd3b1, Cyp17a1, and Srd5a). Silencing of Gata4 expression in mLTC-1 cells was accompanied by reduced production of sex steroid precursors, as documented by mass spectrometric analysis. Comprehensive metabolomic analysis of GATA4-deficient mLTC-1 cells showed alteration of other metabolic pathways, notably glycolysis. GATA4-depleted mLTC-1 cells had reduced expression of glycolytic genes (Hk1, Gpi1, Pfkp, and Pgam1), lower intracellular levels of ATP, and increased extracellular levels of glucose. Our findings suggest that GATA4 plays a pivotal role in Leydig cell function and provide novel insights into metabolic regulation in this cell type.

scholarly journals Serum Concentrations and Gonadal Expression of INSL3 in Eighteen Males With 45,X/46,XY Mosaicism

2021 ◽  
Vol 12 ◽  
Author(s):  
Marie Lindhardt Ljubicic ◽  
Anne Jørgensen ◽  
Lise Aksglaede ◽  
John Erik Nielsen ◽  
Jakob Albrethsen ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Sperm Concentration ◽  
External Genitalia ◽  
Reproductive Hormones ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Cell Hyperplasia ◽  
Tissue Samples ◽  
Median Serum ◽  
Significant Difference

ObjectiveInsulin-like factor 3 (INSL3) is produced in the testes and has been proposed as a circulating biomarker of Leydig cell capacity, but remains undescribed in 45,X/46,XY mosaicism. The aim was to examine serum concentrations and gonadal expression of INSL3 in 45,X/46,XY mosaicism.MethodsRetrospectively collected data from medical records, gonadal tissue samples, and prospectively analyzed serum samples from eighteen male patients with 45,X/46,XY mosaicism (one prepubertal, four testosterone-treated, 13 untreated) were included. Biochemical, clinical, and histological outcomes were evaluated according to serum INSL3 concentrations, quantified by LC-MS/MS methodology, and gonadal INSL3 immunohistochemical expression.ResultsSerum INSL3 concentrations spanned from below to above the reference range. In untreated patients, the median serum INSL3 SD score was -0.80 (IQR: -1.65 to 0.55) and no significant difference was observed between INSL3 and testosterone. There was no clear association between serum INSL3 and External Genitalia Score at diagnosis, spontaneous puberty, or sperm concentration. INSL3 and CYP11A1 expression overlapped, except for less pronounced INSL3 expression in areas with severe Leydig cell hyperplasia. No other apparent links between INSL3 expression and histological outcomes were observed.ConclusionsIn this pilot study, serum INSL3 concentrations ranged and seemed independent of other reproductive hormones and clinical features in males with 45,X/46,XY mosaicism. Discordant expression of INSL3 and CYP11A1 may explain low INSL3 and normal testosterone concentrations in some patients. Further studies are needed to elucidate the divergence between serum INSL3 and testosterone and the potential clinical use of INSL3.

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