Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty
ZHOU Xue-Lian1, FU Jun-Fen1, JIN Ju-Hua2, DONG Guan-Ping1, JIANG You-Jun1, HUANG Ke1, CHEN Xue-Feng1, WU Wei1
Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China
Abstract Objective To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP). Methods Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis. Results There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P< 0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P< 0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P< 0.05), and positively correlated with the levels of leptin and neurokinin B (P< 0.05). Conclusions The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.
About author:: 10.7499/j.issn.1008-8830.2015.08.001
Cite this article:
ZHOU Xue-Lian,FU Jun-Fen,JIN Ju-Hua et al. Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty[J]. CJCP, 2015, 17(8): 763-768.
ZHOU Xue-Lian,FU Jun-Fen,JIN Ju-Hua et al. Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty[J]. CJCP, 2015, 17(8): 763-768.
Euling SY, Herman-Giddens ME, Lee PA, et al. Examination of US puberty-timing data from 1940 to 1994 for secular trends: panel findings[J]. Pediatrics, 2008, 121(3): S172-S191.
[2]
Soriano-Guillen L, Corripio R, Labarta JI, et al. Central precocious puberty in children living in Spain: incidence, prevalence, and influence of adoption and immigration[J]. J Clin Endocrinol Metab, 2010, 95(9): 4305-4313.
[3]
Lee JM, Appugliese D, Kaciroti N, et al. Weight status in young girls and the onset of puberty[J]. Pediatrics, 2007, 119(3): e624-e630.
[4]
Dai YL, Fu JF, Liang L, et al. Association between obesity and sexual maturation in Chinese children: a muticenter study[J]. Int J Obes (Lond), 2014, 38(10): 1312-1316.
[5]
Bordini B, Littlejohn E, Rosenfield RL. Blunted sleep-related luteinizing hormone rise in healthy premenarcheal pubertal girls with elevated body mass index[J]. J Clin Endocrinol Metab, 2009, 94(4): 1168-1175.
[6]
Collins JS, Beller JP, Burt Solorzano C, et al. Blunted day-night changes in luteinizing hormone pulse frequency in girls with obesity: the potential role of hyperandrogenemia[J]. J Clin Endocrinol Metab, 2014, 99(8): 2887-2896.
[7]
Lee HS, Park HK, Ko JH, et al. Impact of body mass index on luteinizing hormone secretion in gonadotropin-releasing hormone stimulation tests of boys experiencing precocious puberty[J]. Neuroendocrinology, 2012, 97(3): 225-231.
[8]
Fu JF, Liang JF, Zhou XL, et al. Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty[J]. Obesity (Silver Spring), 2015, 23(3): 637-643.
[9]
Giabicani E, Allali S, Durand A, et al. Presentation of 493 consecutive girls with idiopathic central precocious puberty: a single-center study[J]. PLoS One, 2013, 8(7): e70931.
Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls[J]. Arch Dis Child, 1969, 44(235): 291-303.
[13]
Greulich WPS. Radiographic atlas of skeletal development of the hand and wrist[M]. 2nd edition. California: Stanford University Press, 1959: 145-150.
[14]
Rosenfield RL, Bordini B. Evidence that obesity and androgens have independent and opposing effects on gonadotropin production from puberty to maturity[J]. Brain Res, 2010, 1364: 186-197.
[15]
Roth LW, Bradshaw-Pierce EL, Allshouse AA, et al. Evidence of GnRH antagonist escape in obese women[J]. J Clin Endocrinol Metab, 2014, 99(5): E871-E875.
[16]
Yeung EH, Zhang C, Albert PS, et al. Adiposity and sex hormones across the menstrual cycle: the BioCycle Study[J]. Int J Obes (Lond), 2013, 37(2): 237-243.
[17]
Chan JL, Matarese G, Shetty GK, et al. Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans[J]. Proc Natl Acad Sci USA, 2006, 103(22): 8481-8486.
[18]
Farooqi IS, Wangensteen T, Collins S, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor[J]. N Engl J Med, 2007, 356(3): 237-247.
[19]
Martos-Moreno GA, Barrios V, Argente J. Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids[J]. Eur J Endocrinol, 2006, 155(3): 429-434.
[20]
Martos-Moreno GA, Chowen JA, Argente J. Metabolic signals in human puberty: effects of over and undernutrition[J]. Mol Cell Endocrinol, 2010, 324(1-2): 70-81.
[21]
Soliman AT, Yasin M, Kassem A. Leptin in pediatrics: a hormone from adipocyte that wheels several functions in children[J]. Indian J Endocrinol Metab, 2012, 16(3): S577-S587.
[22]
Franco JG, Lisboa PC, da Silva Lima N, et al. Resveratrol prevents hyperleptinemia and central leptin resistance in adult rats programmed by early weaning[J]. Horm Metab Res, 2014, 46(10): 728-735.
[23]
Shimizu H, Oh IS, Okada S, et al. Leptin resistance and obesity[J]. Endocr J, 2007, 54(1): 17-26.
[24]
Pan H, Guo J, Su Z. Advances in understanding the interrelations between leptin resistance and obesity[J]. Physiol Behav, 2014, 130: 157-169.
[25]
Pinkney J, Streeter A, Hosking J, et al. Adiposity, chronic inflammation, and the prepubertal decline of sex hormone binding globulin in children: evidence for associations with the timing of puberty (earlybird 58)[J]. J Clin Endocrinol Metab, 2014, 99(9): 3224-3232.
[26]
Birkebaek NH, Lange A, Holland-Fischer P, et al. Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children[J]. Eur J Endocrinol, 2010, 163(6): 895-900.
[27]
Shi J, Li L, Hong J, et al. Genetic variants determining body fat distribution and sex hormone-binding globulin among Chinese female young adults[J]. J Diabetes, 2014, 6(6): 514-518.
[28]
Pilia S, Casini MR, Foschini ML, et al. The effect of puberty on insulin resistance in obese children[J]. J Endocrinol Invest, 2009, 32(5): 401-405.
[29]
Kavanagh K, Espeland MA, Sutton-Tyrrell K, et al. Liver fat and SHBG affect insulin resistance in midlife women: the Study of Women's Health Across the Nation (SWAN)[J]. Obesity (Silver Spring), 2013, 21(5): 1031-1038.
[30]
Topaloglu AK, Reimann F, Guclu M, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction[J]. Nat Genet, 2009, 41(3): 354-358.
[31]
Navarro VM, Castellano JM, McConkey SM, et al. Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat[J]. Am J Physiol Endocrinol Metab, 2011, 300(1): E202-E210.
[32]
Navarro VM, Ruiz-Pino F, Sanchez-Garrido MA, et al. Role of neurokinin B in the control of female puberty and its modulation by metabolic status[J]. J Neurosci, 2012, 32(7): 2388-2397.
[33]
Kinsey-Jones JS, Grachev P, Li XF, et al. The inhibitory effects of neurokinin B on GnRH pulse generator frequency in the female rat[J]. Endocrinology, 2012, 153(1): 307-315.
[34]
Li SY, Li XF, Hu MH, et al. Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat[J]. J Neuroendocrinol, 2014, 26(8): 521-527.
[35]
Topaloglu AK, Tello JA, Kotan LD, et al. Inactivating KISS1 mutation and hypogonadotropic hypogonadism[J]. N Engl J Med, 2012, 366(7): 629-635.
[36]
Teles MG, Bianco SD, Brito VN, et al. A GPR54-activating mutation in a patient with central precocious puberty[J]. N Engl J Med, 2008, 358(7): 709-715.
Pita J, Barrios V, Gavela-Perez T, et al. Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty[J]. Peptides, 2011, 32(9): 1781-1786.
[39]
Roa J, Vigo E, Garcia-Galiano D, et al. Desensitization of gonadotropin responses to kisspeptin in the female rat: analyses of LH and FSH secretion at different developmental and metabolic states[J]. Am J Physiol Endocrinol Metab, 2008, 294(6): E1088-E1096.
[40]
Quennell JH, Howell CS, Roa J, et al. Leptin deficiency and diet-induced obesity reduce hypothalamic kisspeptin expression in mice[J]. Endocrinology, 2011, 152(4): 1541-1550.
[41]
Navarro VM, Gottsch ML, Wu M, et al. Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse[J]. Endocrinology, 2011, 152(11): 4265-4275.
[42]
Garcia-Galiano D, van Ingen Schenau D, Leon S, et al. Kisspeptin signaling is indispensable for neurokinin B, but not glutamate, stimulation of gonadotropin secretion in mice[J]. Endocrinology, 2012, 153(1): 316-328.
