Longitudinal assessment of circulating insulin-like peptide 3 levels in healthy peripubertal girls

Objective: To elucidate the natural course of circulating insulin-like peptide 3 (INSL3) levels according to puberty as well as its relation to other reproductive hormones. Design: Population-based cohort study. Setting: Not applicable. Patient(s): Healthy peripubertal girls (n¼10) examined every 6 months; total number of examinations was 84; median (range) per girl:9 (4–10), including staging of pubertal breast development and blood samples. Intervention(s): None. Main Outcome Measure(s): Serum levels of INSL3, inhibin B, E2, antim€ullerian hormone, LH, and FSH (validated immunoassays), and T and androstenedione (liquid chromatography–tandem mass spectrometry). Result(s): Serum levels of INSL3 varied considerably between girls (range, 0.01–0.27 ng/mL) and within each girl as puberty progressed; intraindividual variation, median (range) 102% (65%–143%). Insulin-like peptide 3 increased in late puberty (B1 to B4þB5); geometric mean 0.03 ng/mL to 0.15 ng/mL. Insulin-like peptide 3 levels reflected markers of large follicles (T, androstendione, inhibin B, and E2) better than markers of small follicles (antim€ullerian hormone), and INSL3 staining was localized in theca interna cells of antral follicles. Conclusion(s): Insulin-like peptide 3 increased in late puberty, albeit inter- and intraindividual variations were substantial. Immunohistochemistry and intraindividual variation, as well as relations to other ovarian hormones, reveal that INSL3 in girls is a unique and specific marker of theca cells surrounding antral follicles. The potential clinical use of INSL3 for evaluation of ovarian function in girls remains to be elucidated

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

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

Pubertal Progression and Reproductive Hormones in Healthy Girls With Transient Thelarche

Abstract Context: Detailed evaluation of pubertal progression in girls from longitudinal studies is sparse, and the phenomenon of transient thelarche (TT), defined as the appearance, regression, and subsequent reappearance of breast buds, in healthy girls remains undescribed. Objective: To describe TT in terms of pubertal progression, growth, genotypes, and reproductive hormones and to apply new puberty nomograms for breast stages, pubic hair, and menarche. Design: A prospective, longitudinal population-based study. Patients or Other Participants: Ninety-eight healthy Danish schoolchildren (Caucasian girls) followed longitudinally as part of the COPENHAGEN Puberty Study were included in the evaluation of TT. A total of 1466 girls from 2 cross-sectional studies were included in the creation of the puberty nomograms. Intervention(s): None. Main Outcome Measure(s): Pubertal progression, specifically thelarche, reproductive hormones, genotype, and growth. Results: Twelve of 98 (12%) girls experienced TT. A larger proportion of girls with TT entered puberty by the pubarche pathway (50%) compared with girls with normal progression (15.4%), P = 0.014. Girls with TT progressed through puberty normally when evaluated using puberty nomograms. Reproductive hormones and growth velocity were lower at the first (transient) thelarche than the second (permanent) thelarche. Conclusion: TT is a frequent phenomenon that appears to be a peripheral occurrence independent of central puberty. It does not appear to affect subsequent pubertal progression as evaluated by our new puberty nomograms. </jats:sec