Augmented frequency and mass of LH discharged per burst are accompanied by marked disorderliness of LH secretion in adolescents with polycystic ovary syndrome

Maria Cecilia García-Rudaz, María Gabriela Ropelato, Maria Eugenia Escobar, Johannes D. Veldhuis, Marta Barontini

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The aim of this study was to quantify pulsatile LH secretion, burst frequency and mass, LH half-life, and the approximate entropy (ApEn) or (dis- ) orderliness of LH release in adolescents with polycystic ovary syndrome (PCOS), combining a high-precision immunofluorimetric LH assay with deconvolution techniques. We sampled LH concentration profiles every 20 min overnight in 12 girls with PCOS (mean ± S.E.M. age 16.4 ± 0.57 years, body mass index (BMI) 24.4 ± 1.6 kg/m2) and 11 eumenorrheic early-follicular- phase controls (mean ± S.E.M. age 16.5 ± 0.47 years, BMI 22.2 ± 1.0 kg/m2). Fasting serum levels of androstenedione, testosterone, 17- hydroxyprogesterone (17-OHP), estrone, estradiol, FSH and sex hormone- binding globulin (SHBG) were determined. Compared with euandrogenic girls, PCOS adolescents had significantly (P < 0.005) elevated serum LH/FSH ratios, 17-OHP, androstenedione, esterone and testosterone levels, decreased SHBG, and similar estradiol. PCOS subjects exhibited a 3-fold higher mean serum LH concentration with almost no overlap with controls (8.8 ± 1.2 and 2.8 ± 0.3 IU/l respectively, P < 0.001). We initially used a conventional serum hormone concentration peak analysis method (Cluster) to evaluate the characteristics of pulsatile LH release. Cluster analysis disclosed a significant increase in serum LH concentration maximal peak height, a higher LH peak frequency and a higher mean serum LH concentration in interpulse nadirs in the PCOS group. Deconvolution analysis of mechanisms underlying the foregoing showed higher frequency in the PCOS group than the controls (7.9 ± 0.4 and 5.7 ± 0.6 pulses/12 h respectively, P < 0.05). The mass of LH released per secretory event was also significantly higher in PCOS subjects than controls (5.4 ± 0.57 and 3.4 ± 0.56 IU/l respectively, P < 0.05). Since the pulsatile production rate is the product of the mean mass of hormone secreted per pulse and the number of pulses per day, we estimated a significantly higher mean pulsatile production rate of (endogenous) LH in the PCOS group (41 ± 4.2 IU/l per day in the PCOS group vs 18 ± 2.3 IU/l per day in the controls, P < 0.01). The mean estimated half-life of endogenous LH disappearance was also significantly higher in patients with PCOS than in controls (110 ± 8.5 and 77 ± 3.7 min respectively, P < 0.01). To quantify the orderliness of LH release, we used ApEn. PCOS patients had remarkably increased disorderliness (higher ApEn) of LH release (1.09 ± 0.04 vs 0.77 ± 0.08 in controls, P = 0.002). Mean serum LH concentration, mass of LH secreted per burst, and LH production rate in PCOS, but not in normal adolescents, correlated positively with androstenedione (P < 0.02, 0.02 and 0.05 respectively). The same parameters also correlated positively with 17-OHP (P < 0.05, 0.02 and 0.05 respectively). Stepwise regression analysis unmasked a negative influence of BMI in PCOS on both mass of LH secreted per burst (r = -0.77, P < 0.005) and LH production rate (r = -0.70, P < 0.01). We conclude that PCOS adolescents secrete LH molecules with amplified frequency and burst mass and with markedly disrupted orderliness. A rise in basal (non-pulsatile) LH release, more basic LH isoforms, and/or a prolongation or asymmetry of the LH secretory burst could account for the apparently prolonged LH half-life. Determining whether disorderliness of the amplified pituitary LH release process is an intrinsic abnormality in PCOS, or reflects androgen excess, may help to clarify the pathophysiology of this oligo-ovulatory syndrome in young women.

Original languageEnglish (US)
Pages (from-to)621-630
Number of pages10
JournalEuropean journal of endocrinology
Volume139
Issue number6
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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