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Horm Metab Res 2012; 44(07): 533-538
DOI: 10.1055/s-0032-1304578
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Sexual Dimorphism on Growth Hormone Secretion after Oral Glucose Administration

E. Outeiriño-Blanco
1   Department of Endocrinology, University Hospital A Coruña, La Coruña, Spain
,
J. Garcia-Buela
2    Department of Laboratory, University Hospital A Coruña, La Coruña, Spain
,
S. Sangiao-Alvarellos
3    Department of Investigation University Hospital A Coruña, La Coruña, Spain
4   Department of Medicine University of A Coruña , La Coruña, Spain
,
I. Brandón
3    Department of Investigation University Hospital A Coruña, La Coruña, Spain
,
L. Pena
3    Department of Investigation University Hospital A Coruña, La Coruña, Spain
,
S. Pertega-Diaz
5   Clinical Epidemiology and Biostatistics Unit, University Hospital A Coruña, La Coruña, Spain
,
T. Martinez
1   Department of Endocrinology, University Hospital A Coruña, La Coruña, Spain
,
F. Cordido
1   Department of Endocrinology, University Hospital A Coruña, La Coruña, Spain
3    Department of Investigation University Hospital A Coruña, La Coruña, Spain
4   Department of Medicine University of A Coruña , La Coruña, Spain
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Publikationsverlauf

received 21. September 2011

accepted 19. Januar 2012

Publikationsdatum:
16. Februar 2012 (online)

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Abstract

Sexual dimorphism of GH secretion is unclear in humans. There is evidence that oral glucose (OG) administration initially decreases and subsequently stimulates GH secretion. Our aim was to study fasting GH concentrations and their response to OG administration in obese and healthy women and men, in order to elucidate the mechanism of sexual dimorphism of GH secretion and the possible contribution of ghrelin. We selected 33 women and 11 men as obese and healthy subjects. After an overnight fast, 75 g of oral glucose were administered; glucose, insulin, ghrelin, and PYY1–36 were obtained at baseline and during 300 min. Fasting GH (μg/l) was higher in women than men; 1.3±0.3 vs. 0.2±0.1, p=0.009, for women and men, respectively. The area under the curve between 0 and 150 min (AUC) of GH (μg/l · min) was higher in women than men; 98.2±25.9 vs. 41.5±28.6, p=0.002, for women and men, respectively. The AUC of total ghrelin (pg/ml · min, mean±SEM) between 0 and 150 min was borderline and significantly higher in women than men; 128 562.3±8 335.9 vs. 98 839.1±7 668.6, p=0.069, for women and men, respectively. Several initial time points were higher in women than men. Glucose, insulin, and PYY1–36 were similar in women and men after OG. There were significant correlations between indices of post-oral glucose GH and ghrelin secretion. Fasting and initial GH secretion is higher in women than men, in contrast to peak and late GH secretion, which is similar in both cases. Sexual dimorphism in the regulation of GH secretion probably involves ghrelin.

Key words

GH - ghrelin - oral glucose - sexual dimorphism
 

  • References

  • 1 Gatford KL, Egan AR, Clarke IJ, Owens PC. Sexual dimorphism of the somatotrophic axis. J Endocrinol 1998; 157: 373-389
    CrossrefPubMedSuche in Google Scholar
  • 2 Jaffe CA, Ocampo-Lim B, Guo W, Krueger K, Sughara I, DeMott-Friberg R, Bermann M, Barkan AL. Regulatory mechanisms of growth hormone secretion are sexually dimorphic. J Clin Invest 1998; 102: 153-164
    CrossrefPubMedSuche in Google Scholar
  • 3 Jessup SK, Dimaraki EV, Symons KV, Barkan AL. Sexual dimorphism of growth hormone (GH) regulation in humans: endogenous GH-releasing hormone maintains basal GH in women but not in men. J Clin Endocrinol Metab 2003; 88: 4776-4780
    CrossrefPubMedSuche in Google Scholar
  • 4 Veldhuis JD, Roelfsema F, Keenan DM, Pincus S. Gender, Age, body mass index, and IGF-I individually and jointly determine distinct GH dynamics: Analyses in one hundred healthy adults. J Clin Endocrinol Metab 2011; 96: 115-121
    CrossrefPubMedSuche in Google Scholar
  • 5 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 999; 402: 656-660
    PubMed
  • 6 Alvarez-Castro P, Isidro ML, Garcia-Buela J, Leal-Cerro A, Broglio F, Tassone F, Ghigo E, Dieguez C, Casanueva FF, Cordido F. Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients. Clin Endocrinol (Oxf) 2004; 61: 250-255
    CrossrefPubMedSuche in Google Scholar
  • 7 Alaioubi B, Mann K, Petersenn S. Diagnosis of growth hormone deficiency in adults: provocative testing with GHRP6 in comparison to the insulin tolerance test. Horm Metab Res 2009; 41: 238-243
    Thieme ConnectPubMedSuche in Google Scholar
  • 8 Lanfranco F, Motta G, Baldi M, Gasco V, Grottoli S, Benso A, Broglio F, Ghigo E. Ghrelin and anterior pituitary function. Front Horm Res 2010; 38: 206-211
    PubMedSuche in Google Scholar
  • 9 Perez-Fontan M, Cordido F, Rodriguez-Carmona A, Garcia-Naveiro R, Isidro ML, Villaverde P, Garcia-Buela J. Acute plasma ghrelin and leptin responses to oral feeding or intraperitoneal hypertonic glucose-based dialysate in patients with chronic renal failure. Kidney Int 2005; 68: 2877-2885
    CrossrefPubMedSuche in Google Scholar
  • 10 Misra M, Miller KK, Kuo K, Griffin K, Stewart K, Hunter E, herzog DB, Klibanski A. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiol Endocrinol Metab 2005; 289: E347-E356
    CrossrefPubMedSuche in Google Scholar
  • 11 Nass R, Farhy LS, Liu J, Prudom CE, Johnson ML, Veldhuis J, Pezzoli SS, Oliveri MC, Gaylinn BD, Geysen HM, Thorner MO. Evidence for acyl-ghrelin modulation of growth hormone release in the fed state. J Clin Endocrinol Metab 2008; 93: 1988-1994
    CrossrefPubMedSuche in Google Scholar
  • 12 Outeirino-Blanco E, Garcia-Buela J, Sangiao-Alvarellos S, Pertega-Diaz S, Martinez-Ramonde T, Cordido F. Growth Hormone, Ghrelin and Peptide YY Secretion after Oral Glucose Administration in Healthy and Obese Women. Horm Metab Res 2011; 43: 580-586
    Thieme ConnectPubMedSuche in Google Scholar
  • 13 Ingelsson E, Larson MG, Yin X, Wang TJ, Meigs JB, Lipinska I, Benjamin EJ, Keaney JF, Vasan RS. Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample. J Clin Endocrinol Metab 2008; 93: 3149-3157
    CrossrefPubMedSuche in Google Scholar
  • 14 Barkan AL, Dimaraki EV, Jessup SK, Symons KV, Ermolenko M, Jaffe CA. Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels. J Clin Endocrinol Metab 2003; 88: 2180-2184
    CrossrefPubMedSuche in Google Scholar
  • 15 Resmini E, Andraghetti G, Rebora A, Cordera R, Vera L, Giusti M, Minuto F, Ferone D. Leptin, ghrelin, and adiponectin evaluation in transsexual subjects during hormonal treatments. J Androl 2008; 29: 580-585
    CrossrefPubMedSuche in Google Scholar
  • 16 Lloyd B, Ravi P, Mendes N, Klibanski A, Misra M. Peptide YY levels across pubertal stages and associations with growth hormone. J Clin Endocrinol Metab 2010; 95: 2957-2962
    CrossrefPubMedSuche in Google Scholar
  • 17 Grottoli S, Procopio M, Maccario M, Zini M, Oleandr SE, Tassone F, Valcavi R, Ghigo E. In obesity, glucose load loses its early inhibitory, but maintains its late stimulatory, effect on somatotrope secretion. J Clin Endocrinol Metab 1997; 82: 2261-2265
    CrossrefPubMedSuche in Google Scholar
  • 18 Shiiya T, Nakazato M, Mizuta M, date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002; 87: 240-244
    CrossrefPubMedSuche in Google Scholar
  • 19 Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev 2005; 85: 495-522
    CrossrefPubMedSuche in Google Scholar
  • 20 Benedini S, Codella R, Caumo A, Marangoni F, Luzi L. Different circulating ghrelin responses to isoglucidic snack food in healthy individuals. Horm Metab Res 2011; 43: 135-140
    Thieme ConnectPubMedSuche in Google Scholar
  • 21 Cordido F, Garcia-Buela J, Sangiao-Alvarellos S, Martinez T, Vidal O. The decreased growth hormone response to growth hormone releasing hormone in obesity is associated to cardiometabolic risk factors. Mediators Inflamm 2010; 2010: 434562
    PubMedSuche in Google Scholar
  • 22 Sangiao-Alvarellos S, Vazquez MJ, Varela L, Nogueiras R, Saha AK, Cordido F, Lopez M, Dieguez C. Central ghrelin regulates peripheral lipid metabolism in a growth hormone-independent fashion. Endocrinology 2009; 150: 4562-4574
    CrossrefPubMedSuche in Google Scholar
  • 23 Sangiao-Alvarellos S, Varela L, Vazquez MJ, Da Boit K, Saha AK, Cordido F, Dieguez C, Lopez M. Influence of Ghrelin and growth hormone deficiency on AMP-activated protein kinase and hypothalamic lipid metabolism. J Neuroendocrinol 2010; 22: 543-556
    CrossrefPubMedSuche in Google Scholar
  • 24 Sangiao-Alvarellos S, Helmling S, Vazquez MJ, Klussmann S, Cordido F. Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism. Mol Cell Endocrinol 2011; 335: 177-188
    CrossrefPubMedSuche in Google Scholar
  • 25 Osterstock G, Escobar P, Mitutsova V, Gouty-Colomer LA, Fontanaud P, Molino F, Fehrentz JA, Carmignac D, Martinez J, Guerineau NC, Robinson IC, Mollard P, Mery PF. Ghrelin stimulation of growth hormone-releasing hormone neurons is direct in the arcuate nucleus. PLoS ONE 2010; 5: e9159
    CrossrefPubMedSuche in Google Scholar
  • 26 Nass R, Pezzoli SS, Oliveri MC, Patrie JT, Harrell FE, Clasey JL, Heymsfield SB, Bach MA, Vance ML, Thorner MO. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med 2008; 149: 601-611
    PubMedSuche in Google Scholar
  • 27 Pantel J, Legendre M, Nivot S, Morisset S, Vie-Luton MP, le Bouc Y, Epelbaum J, Amselem S. Recessive isolated growth hormone deficiency and mutations in the ghrelin receptor. J Clin Endocrinol Metab 2009; 94: 4334-4341
    CrossrefPubMedSuche in Google Scholar
  • 28 Zhao TJ, Liang G, Li RL, Xie X, Sleeman MW, Murphy AJ, Valenzuela DM, Yancopoulos GD, Goldstein JL, Brown MS. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci USA 2010; 107: 7467-7472
    CrossrefPubMedSuche in Google Scholar
  • 29 Ji XS, Chen SL, Jiang YL, Xu TJ, Yang JF, Tian YS. Growth differences and differential expression analysis of pituitary adenylate cyclase activating polypeptide (PACAP) and growth hormone-releasing hormone (GHRH) between the sexes in half-smooth tongue sole Cynoglossus semilaevis. Gen Comp Endocrinol 2011; 170: 99-109
    CrossrefPubMedSuche in Google Scholar
  • 30 Diz-Lois MT, Garcia-Buela J, Suarez F, Sangiao-Alvarellos S, Vidal O, Cordido F. Fasting and postprandial plasma ghrelin levels are decreased in patients with liver failure previous to liver transplantation. Endocrine 2009; 35: 467-476
    CrossrefPubMedSuche in Google Scholar
  • 31 Diz-Lois MT, Garcia-Buela J, Suarez F, Sangiao-Alvarellos S, Vidal O, Cordido F. Altered fasting and postprandial plasma ghrelin levels in patients with liver failure are normalized after liver transplantation. Eur J Endocrinol 2010; 163: 609-616
    CrossrefPubMedSuche in Google Scholar
  • 32 Rodriguez-Carmona A, Perez Fontan M, Cordido F, Garcia Falcon T, Garcia-Buela J. Hyperleptinemia is not correlated with markers of protein malnutrition in chronic renal failure. A cross-sectional study in predialysis, peritoneal dialysis and hemodialysis patients. Nephron 2000; 86: 274-280
    CrossrefPubMedSuche in Google Scholar
  • 33 Peino R, Fernandez Alvarez J, Penalva A, Considine RV, Rodriguez-Segade S, Rodriguez-Garcia J, Cordido F, Casanueva FF, Dieguez C. Acute changes in free-fatty acids (FFA) do not alter serum leptin levels. J Endocrinol Invest 1998; 21: 526-530
    PubMedSuche in Google Scholar
  • 34 Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A, Boyadjian R, Jinagouda SD, el-Tawil K, Rude RK, Kamdar V. Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab 1997; 82: 579-584
    CrossrefPubMedSuche in Google Scholar
  • 35 Kennedy A, Gettys TW, Watson P, Wallace P, Ganaway E, Pan Q, Garvey WT. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab 1997; 82: 1293-1300
    CrossrefPubMedSuche in Google Scholar
  • 36 Guerra B, Fuentes T, Delgado-Guerra S, Guadalupe-Grau A, Olmedillas H, Santana A, Ponce-Gonzalez JG, Dorado C, Calbet JA. Gender dimorphism in skeletal muscle leptin receptors, serum leptin and insulin sensitivity. PLoS ONE 2008; 3: e3466
    CrossrefPubMedSuche in Google Scholar
  • 37 Alvarez-Castro P, Sangiao-Alvarellos S, Brandon-Sanda I, Cordido F. Endocrine function in obesity. Endocrinol Nutr 2011; 58: 422-432
    CrossrefPubMedSuche in Google Scholar
  • 38 Ondrak KS, McMurray RG, Hackney AC, Harrell JS. Interrelationships among changes in leptin, insulin, cortisol and growth hormone and weight status in youth. J Clin Res Pediatr Endocrinol 2011; 3: 22-28
    CrossrefPubMedSuche in Google Scholar
  • 39 Liu Y, Zhong Y, Pei J, Zhu Y, Hu Y, Chi S, Kaye AD. Inhibitory effect of leptin on growth hormone secretion of GH3 cells: involvement of cell proliferation, apoptosis and intracellular free Ca2. Cytokine 2009; 46: 245-250
    CrossrefPubMedSuche in Google Scholar
  • 40 Roubenoff R, Rall LC, Veldhuis JD, Kehayias JJ, Rosen C, Nicolson M, Lundgren N, Reichlin S. The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin. J Clin Endocrinol Metab 1998; 83: 1502-1506
    CrossrefPubMedSuche in Google Scholar
  • 41 Roemmler J, Otto B, Arafat AM, Bidlingmaier M, Schopohl J. Influence of pegvisomant on serum ghrelin and leptin levels in acromegalic patients. Eur J Endocrinol 2010; 163: 727-734
    CrossrefPubMedSuche in Google Scholar
  • 42 Roemmler J, Gockel A, Otto B, Bidlingmaier M, Schopohl J. Effects on metabolic variables after 12-month treatment with a new once-a-week sustained-release recombinant growth hormone (GH: LB03002) in patients with GH deficiency (GHD). Clin Endocrinol (Oxf) 2012; 76: 88-95
    CrossrefPubMedSuche in Google Scholar
  • 43 Yamashita S, Melmed S. Insulin regulation of rat growth hormone gene transcription. J Clin Invest 1986; 78: 1008-1014
    CrossrefPubMedSuche in Google Scholar
  • 44 Clasey JL, Weltman A, Patrie J, Weltman JY, Pezzoli S, Bouchard C, Thorner MO, Hartman ML. Abdominal visceral fat and fasting insulin are important predictors of 24-h GH release independent of age, gender, and other physiological factors. J Clin Endocrinol Metab 2001; 86: 3845-3852
    CrossrefPubMedSuche in Google Scholar
  • 45 McLaughlin T, Abbasi F, Lamendola C, Frayo RS, Cummings DE. Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 2004; 89: 1630-1635
    CrossrefPubMedSuche in Google Scholar
  • 46 Hotta M, Ohwada R, Katakami H, Shibasaki T, Hizuta N, Takano K. Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa. J Clin Endocrinol Metab 2004; 89: 5707-5712
    CrossrefPubMedSuche in Google Scholar
  • 47 Blatnik M, Soderstrom CI. A practical guide for the stabilization of acylghrelin in human blood collections. Clin Endocrinol (Oxf) 2011; 74: 325-331
    CrossrefPubMedSuche in Google Scholar