Higher ghrelin and lower leptin secretion are associated with lower LH secretion in young amenorrheic athletes compared with eumenorrheic athletes and controls.

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Abstract

Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation to leptin or ghrelin secretory dynamics in adolescent and young adult athletes. We hypothesized that 1) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and nonathletes and 2) higher ghrelin and lower leptin would be associated with lower LH secretion. This was a cross-sectional study. We examined ghrelin and leptin secretory patterns (over 8 h, from 11 PM to 7 AM) in relation to LH secretory patterns in AA, EA, and nonathletes aged 14-21 yr. Ghrelin and leptin were assessed every 20 min and LH every 10 min. Groups did not differ for age, bone age, or BMI. However, fat mass was lower in AA than in EA and nonathletes. AA had lower LH and higher ghrelin pulsatile secretion and AUC than nonathletes and lower leptin pulsatile secretion and AUC than EA and nonathletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. We conclude that higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.

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Bone microarchitecture is impaired in adolescent amenorrheic athletes compared with eumenorrheic athletes and nonathletic controls.

Nara Mendes, Melissa Russell, William E. Ackerman … (2011)

Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15-21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18-24% of the variability in tibial trabecular number and separation. In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA.

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Objective and subjective measures of sedentary behavior and physical activity.

Catrine Tudor-Locke, Gillian B. Ainsworth, Richard T. Hart (2011)

To examine the convergent validity of the ActiGraph and activPAL accelerometers with the Bouchard Activity Record (BAR) in adults. Sedentary behavior and walking were evaluated in all instruments; standing and moderate-to-vigorous physical activity (MVPA) was evaluated only in those that detected such variables. Thirty-two participants wore the accelerometers and completed the BAR concurrently for 1 d. Descriptive statistics and delta values were reported for all instruments. Summary time spent in sedentary behavior and walking was compared between all instruments using repeated-measures ANOVA. Dependent t-tests were used to analyze summary time in 1) standing between activPAL and BAR and 2) MVPA between ActiGraph and BAR. Bland-Altman plots were interpreted for systematic bias. On a detailed level, concurrent time interval data were compared using mean percent agreement and κ statistics. There was a significant difference found in summary time spent in sedentary behavior apparent between ActiGraph and activPAL as well as between ActiGraph and BAR. There was also a significant difference detected in time spent in walking, apparent between ActiGraph and activPAL, and between ActiGraph and BAR. In the time interval analysis, mean percent agreement ranged from 54.0% (for walking detected by ActiGraph and activPAL) to 86.7% (for MVPA by ActiGraph and BAR). κ values ranged from 0.25 (for walking by ActiGraph and activPAL) to 0.70 (for sedentary behavior between activPAL and BAR). Differences were also found in standing and MVPA. The activPAL and BAR showed convergence on both summary and concurrent time interval levels in both sedentary behavior and walking. The comparative discordance between activPAL and BAR with ActiGraph was likely a function of different approaches used to distinguish sedentary behavior from walking.

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Effects of ghrelin on Kisspeptin mRNA expression in the hypothalamic medial preoptic area and pulsatile luteinising hormone secretion in the female rat.

Sarah Forbes, Xiao Li, James S. Kinsey-Jones … (2009)

The orexigenic gut peptide ghrelin negatively modulates the hypothalamic-pituitary-gonadal (HPG) axis. Hyperghrelinaemia results during negative energy balance, a state often associated with delayed puberty and disrupted fertility, whilst exogenous ghrelin suppresses pulsatile luteinising hormone (LH) secretion. The recent identification of kisspeptin (Kiss1) and its G protein-coupled receptor (GPR)54 (Kiss1r) as an essential component of the HPG axis controlling gonadotrophin secretion raises the possibility that kisspeptin-Kiss1r signalling may play a critical role in the transduction of ghrelin-induced suppression of LH. Ovariectomised oestrogen-replaced rats were implanted with intravenous catheters and blood samples collected for detection of LH pulses prior to and after intravenous administration of ghrelin (3nM/250 microl) or saline (250 microl) during ad libitum feeding or after overnight fasting. Quantitative RT-PCR was used to determine Kiss1 and Kiss1r mRNA levels in brain punches of the key hypothalamic sites regulating gonadotrophin secretion, the medial preoptic area (mPOA) and arcuate nucleus (ARC), collected 6h following administration of ghrelin. Ghrelin significantly lowered LH pulse frequency in fed rats, an effect significantly enhanced by food deprivation. Fasting, ghrelin or their combination down-regulated Kiss1, without affecting Kiss1r, expression in the mPOA, and affected the expression of neither in the ARC. Considering the pivotal role for kisspeptin signalling in the activation of the HPG axis, the ability of ghrelin to down-regulate Kiss1 expression in mPOA may be a contributing factor in ghrelin-related suppression of pulsatile LH secretion.