All Outputs (71)

Maternal, childhood and adolescent influences on Leydig cell functional capacity and circulating INSL3 concentration in young adults: Importance of childhood infections and body mass index (2025)
Journal Article
Ivell, R., Tilumcu, B., Alhujaili, W., & Anand‐Ivell, R. (2025). Maternal, childhood and adolescent influences on Leydig cell functional capacity and circulating INSL3 concentration in young adults: Importance of childhood infections and body mass index. Andrology, https://doi.org/10.1111/andr.70091

Background: The constitutive Leydig cell hormone insulin-like peptide 3 (INSL3) is considered a good estimate of the adult Leydig cell functional capacity and appears to remain relatively consistent throughout adult male life, only gradually declinin... Read More about Maternal, childhood and adolescent influences on Leydig cell functional capacity and circulating INSL3 concentration in young adults: Importance of childhood infections and body mass index.

Defining the end of puberty in boys: INSL3 and the acute determinants of adult Leydig-cell functional capacity (2025)
Journal Article
Tulumcu, B., Ivell, R., Alhujaili, W., & Anand-Ivell, R. (2025). Defining the end of puberty in boys: INSL3 and the acute determinants of adult Leydig-cell functional capacity. Frontiers in Endocrinology, 16, Article 1574760. https://doi.org/10.3389/fendo.2025.1574760

Introduction:

Testicular Leydig cells are responsible for producing almost all the testosterone required by men throughout the lifespan, with reduced testosterone (hypogonadism) correlating with age-linked morbidity and mortality. Leydig cells de... Read More about Defining the end of puberty in boys: INSL3 and the acute determinants of adult Leydig-cell functional capacity.

Oxytocin (2024)
Book Chapter
Anand-Ivell, R., Ludwig, M., Tribe, R., & Ivell, R. (2024). Oxytocin. In Reference Module in Biomedical Sciences. Elsevier. https://doi.org/10.1016/B978-0-443-21477-6.00121-8

The small peptide hormone oxytocin has long been recognized as a key factor in the natural induction of the birth process at the end of pregnancy, as well as in the release of milk upon suckling by the infant. It has additional roles within the brain... Read More about Oxytocin.

Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold (2024)
Journal Article
Anand-Ivell, R., Heng, K., Antonio, L., Bartfai, G., Casanueva, F. F., Maggi, M., O’Neill, T. W., Punab, M., Rastrelli, G., Slowikowska-Hilczer, J., Tournoy, J., Vanderschueren, D., Wu, F. C., Huhtaniemi, I. T., & Ivell, R. (2024). Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold. Aging Male, 27(1), Article 2346322. https://doi.org/10.1080/13685538.2024.2346322

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of bi... Read More about Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold.

INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis (2024)
Journal Article
Anand-Ivell, R., Coutinho, A. R., Dai, Y., England, G., Goericke-Pesch, S., & Ivell, R. (2024). INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis. Animals, 14(5), Article 675. https://doi.org/10.3390/ani14050675

Insulin-like peptide 3 (INSL3) is a constitutive product of mature, adult-type Leydig cells of the testes and consequently in most mammals is an ideal biomarker with which to monitor pubertal development. A new heterologous time-resolved fluorescence... Read More about INSL3 Variation in Dogs Following Suppression and Recovery of the HPG Axis.

Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men (2022)
Journal Article
Abbara, A., Koysombat, K., Phylactou, M., Chia Eng, P., Clarke, S., Comninos, A. N., Yang, L., Izzi-Engbeaya, C., Hanassab, S., Smith, N., Jayasena, C. N., Xu, C., Quinton, R., Pitteloud, N., Binder, G., Anand-Ivell, R., Ivell, R., & Dhillo, W. S. (2022). Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men. Frontiers in Endocrinology, 13, Article 1076984. https://doi.org/10.3389/fendo.2022.1076984

Background: Delayed puberty in males is almost invariably associated with constitutional delay of growth and puberty (CDGP) or congenital hypogonadotrophic hypogonadism (CHH). Establishing the cause at presentation is challenging, with “red flag” fea... Read More about Insulin-like peptide 3 (INSL3) in congenital hypogonadotrophic hypogonadism (CHH) in boys with delayed puberty and adult men.

The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort (2022)
Journal Article
Ivell, R., Heng, K., Severn, K., Antonio, L., Bartfai, G., Casanueva, F. F., Huhtaniemi, I. T., Giwercman, A., Maggi, M., O’Connor, D. B., O’Neill, T. W., Punab, M., Rastrelli, G., Slowikowska-Hilczer, J., Tournoy, J., Vanderschueren, D., Wu, F. C. W., & Anand-Ivell, R. (2022). The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort. Frontiers in Endocrinology, 13, Article 1016107. https://doi.org/10.3389/fendo.2022.1016107

Background: Insulin-like peptide 3 (INSL3) is a constitutive hormone secreted in men by the mature Leydig cells of the testes. It is an accurate biomarker for Leydig cell functional capacity, reflecting their total cell number and differentiation sta... Read More about The Leydig cell biomarker INSL3 as a predictor of age-related morbidity: Findings from the EMAS cohort.

Influence on the adult male Leydig cell biomarker insulin-like peptide 3 of maternal exposure to estrogenic and anti-androgenic endocrine disrupting compound mixtures: A retrospective study (2022)
Journal Article
Ivell, R., Vinggaard, A. M., Soyama, H., & Anand-Ivell, R. (2022). Influence on the adult male Leydig cell biomarker insulin-like peptide 3 of maternal exposure to estrogenic and anti-androgenic endocrine disrupting compound mixtures: A retrospective study. Andrologia, 54(11), Article e14566. https://doi.org/10.1111/and.14566

Insulin-like peptide 3 (INSL3) is a peptide biomarker secreted specifically by the mature Leydig cells of the testes. It is constitutive, has low within-individual variance, and effectively measures the functional capacity of Leydig cells to make tes... Read More about Influence on the adult male Leydig cell biomarker insulin-like peptide 3 of maternal exposure to estrogenic and anti-androgenic endocrine disrupting compound mixtures: A retrospective study.

Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort (2022)
Journal Article
Anand-Ivell, R., Heng, K., Severn, K., Antonio, L., Bartfai, G., Casanueva, F. F., Huhtaniemi, I. T., Giwercman, A., Maggi, M., O'Neill, T. W., Punab, M., Rastrelli, G., Slowikowska‐Hilczer, J., Tournoy, J., Vanderschueren, D., Wu, F. C., & Ivell, R. (2022). Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort. Andrology, 10(7), 1328-1338. https://doi.org/10.1111/andr.13220

Background: Aging in men is accompanied by a broad range of symptoms, including sexual dysfunction, cognitive and musculoskeletal decline, obesity, type 2 diabetes, cardiovascular disease and hypertension, organ degeneration/failure, and increasing n... Read More about Association of age, hormonal, and lifestyle factors with the Leydig cell biomarker INSL3 in aging men from the European Male Aging Study cohort.

Expression and Role of INSL3 in the Fetal Testis (2022)
Journal Article
Ivell, R., Mamsen, L. S., Andersen, C. Y., & Anand-Ivell, R. (2022). Expression and Role of INSL3 in the Fetal Testis. Frontiers in Endocrinology, 13, Article 868313. https://doi.org/10.3389/fendo.2022.868313

Insulin-like peptide 3 (INSL3) is a small peptide hormone of the insulin-relaxin family which is produced and secreted by the fetal Leydig cells in the testes only. It appears to be undetectable in female fetuses. In the human fetus INSL3 synthesis b... Read More about Expression and Role of INSL3 in the Fetal Testis.

Maternal exposure to dibutyl phthalate (Dbp) or diethylstilbestrol (des) leads to long-term changes in hypothalamic gene expression and sexual behavior (2021)
Journal Article
Hunter, D., Heng, K., Mann, N., Anand-Ivell, R., & Ivell, R. (2021). Maternal exposure to dibutyl phthalate (Dbp) or diethylstilbestrol (des) leads to long-term changes in hypothalamic gene expression and sexual behavior. International Journal of Molecular Sciences, 22(8), 1-14. https://doi.org/10.3390/ijms22084163

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl pht... Read More about Maternal exposure to dibutyl phthalate (Dbp) or diethylstilbestrol (des) leads to long-term changes in hypothalamic gene expression and sexual behavior.

The Physiology of Reproduction – Quo vadis? (2021)
Journal Article
Ivell, R., & Anand-Ivell, R. (2021). The Physiology of Reproduction – Quo vadis?. Frontiers in Physiology, 12, Article 650550. https://doi.org/10.3389/fphys.2021.650550

The reproductive system in males and females reflects a highly dynamic underlying physiology. Yet our current understanding of this system is still largely based upon relatively simplistic snapshots of individual component cells and tissues. Gamete p... Read More about The Physiology of Reproduction – Quo vadis?.

Male seminal parameters are not associated with Leydig cell functional capacity in men (2021)
Journal Article
Anand‐Ivell, R., Tremellen, K., Soyama, H., Enki, D., & Ivell, R. (2021). Male seminal parameters are not associated with Leydig cell functional capacity in men. Andrology, 9(4), 1126-1136. https://doi.org/10.1111/andr.13001

Background: Insulin-like peptide 3 (INSL3) is a constitutive, secreted peptide produced in the male uniquely by the Leydig cells of the testes. It is a biomarker for Leydig cell functional capacity, which is a measure of the numbers and differentiati... Read More about Male seminal parameters are not associated with Leydig cell functional capacity in men.

Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism (2020)
Journal Article
Abbara, A., Eng, P. C., Phylactou, M., Clarke, S. A., Mills, E., Chia, G., Yang, L., Izzi-Engbeaya, C., Smith, N., Jayasena, C. N., Comninos, A. N., Anand-Ivell, R., Rademaker, J., Xu, C., Quinton, R., Pitteloud, N., & Dhillo, W. S. (2021). Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism. Neuroendocrinology, 111(12), 1176-1186. https://doi.org/10.1159/000513248

Background: Hypogonadotropic hypogonadism (HH) is hypogonadism due to either hypothalamic or pituitary dysfunction. While gonadotropin-releasing hormone (GnRH) can directly test pituitary function, no specific test of hypothalamic function exists. Ki... Read More about Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism.

Physiology and evolution of the INSL3/RXFP2 hormone/receptor system in higher vertebrates (2020)
Journal Article
Ivell, R., Alhujaili, W., Kohsaka, T., & Anand-Ivell, R. (2020). Physiology and evolution of the INSL3/RXFP2 hormone/receptor system in higher vertebrates. General and Comparative Endocrinology, 299, Article 113583. https://doi.org/10.1016/j.ygcen.2020.113583

© 2020 Elsevier Inc. Although the insulin-like peptide hormone INSL3 and its cognate receptor RXFP2 (relaxin-family peptide receptor 2) have existed throughout chordate evolution, their physiological diversification appears to be linked closely with... Read More about Physiology and evolution of the INSL3/RXFP2 hormone/receptor system in higher vertebrates.

Effects of acute hCG stimulation on serum INSL3 and 25‐OH vitamin D in Klinefelter syndrome (2020)
Journal Article
Santi, D., Ivell, R., Anand‐Ivell, R., De Toni, L., Fanelli, F., Mezzullo, M., Pelusi, C., Pagotto, U., Belli, S., Granata, A. R. M., Roli, L., Rochira, V., Trenti, T., Ferlin, A., & Simoni, M. (2020). Effects of acute hCG stimulation on serum INSL3 and 25‐OH vitamin D in Klinefelter syndrome. Andrology, https://doi.org/10.1111/andr.12851

© 2020 American Society of Andrology and European Academy of Andrology Background: It has recently been suggested that the hypergonadotropic hypogonadism characterizing Klinefelter syndrome (KS) might not be due to a steroidogenic dysfunction per se,... Read More about Effects of acute hCG stimulation on serum INSL3 and 25‐OH vitamin D in Klinefelter syndrome.

Prepubertal nutrition alters Leydig cell functional capacity and timing of puberty (2019)
Journal Article
Anand-Ivell, R., Byrne, C. J., Arnecke, J., Fair, S., Lonergan, P., Kenny, D. A., & Richard, I. (2019). Prepubertal nutrition alters Leydig cell functional capacity and timing of puberty. PLoS ONE, 14(11), Article e0225465. https://doi.org/10.1371/journal.pone.0225465

Leydig cell functional capacity reflects the numbers and differentiation status of the steroidogenic Leydig cells in the testes and becomes more or less fixed in early adulthood with the final establishment of the hypothalamo-pituitary-gonadal (HPG)... Read More about Prepubertal nutrition alters Leydig cell functional capacity and timing of puberty.

Insulin-Like Peptide 3 (INSL3) (2018)
Book Chapter
Anand-Ivell, R., & Ivell, R. (2018). Insulin-Like Peptide 3 (INSL3). In I. Huhtaniemi, & L. Martini (Eds.), Encyclopedia of Endocrine Diseases (793-806). (Second). Elsevier. https://doi.org/10.1016/B978-0-12-801238-3.65735-5

© 2019 Elsevier Inc. Insulin-like peptide 3 (INSL3) is a major secretory product of the steroidogenic Leydig cells of the testes in the fetus as well as in the adult. It is a constitutive product of the mature Leydig cells and hence acts as an excell... Read More about Insulin-Like Peptide 3 (INSL3).

Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive physiology (2018)
Journal Article
Ivell, R., & Anand-Ivell, R. (2018). Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive physiology. Human Reproduction Update, 24(6), 639-651. https://doi.org/10.1093/humupd/dmy029

BACKGROUND
Insulin-like peptide 3 (INSL3) is a member of the relaxin family of neohormones which has evolved to address specifically mammalian aspects of reproduction related to viviparity and internal fertilization. It was originally identified as... Read More about Insulin-like peptide 3 (INSL3) is a major regulator of female reproductive physiology.

Testicular function and bone in young men with severe childhood-onset obesity. (2018)
Journal Article
Anand-Ivell, R., Ivell, R., Laakso, S., Viljakainen, H., Lipsanen-Nyman, M., Turpeinen, U., Ivaska, K. K., & Mäkitie, O. (2018). Testicular function and bone in young men with severe childhood-onset obesity. Hormone Research in Paediatrics, 89(6), 442–449. https://doi.org/10.1159/000489818

Background: Previous studies suggest increased risk for hypoandrogenism and fractures in men with obesity. We aimed to describe the effects of severe childhood-onset obesity on the cross talk between metabolic state, testes and skeleton at late puber... Read More about Testicular function and bone in young men with severe childhood-onset obesity..