Abstract
Age and gender impact the full repertoire of neurohormone systems, including most prominently the somatotropic, gonadotropic and lactotropic axes. For example, daily GH production is approximately 2-fold higher in young women than men and varies by 20-fold by sexual developmental status and age. Deconvolution estimates of 24-h GH secretion rates exceed 1200 ώg/m2 in adolescents and fall below 60 ώg/m2 in aged individuals. The present overview highlights plausible factors driving such lifetime variations in GH availability, i.e., estrogen, aromatizable androgen, hypothalamic peptides and negative feedback by GH and IGF-I. In view of the daunting complexity of potential neuromodulatory signals, we underline the utility of conceptualizing a simplified three-peptide regulatory ensemble of GHRH, GHRP (ghrelin) and somatostatin. The foregoing signals act as individual and conjoint mediators of adaptive GH control. Regulation is enforced at 3-fold complementary time scales, which embrace pulsatile (burst-like), entropic (orderly) and 24-h rhythmic (nycthemeral) modes of GH release. This unifying platform offers a convergent perspective of multivalent control of GH outflow.
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Veldhuis JD. Nature of altered pulsatile hormone release and neuroendocrine network signalling in human ageing: clinical studies of the somatotropic, gonadotropic, corti-cotropic, and insulin axes. 2000 Mechanisms and Biologica Significance of Pulsatile Hormone Secretion. John Wiley & Sons Ltd 2000, 163–89.
Giustina A, Veldhuis JD. Pathophysiology of the neu-roregulation of growth hormone secretion in experimenta animals and the human. Endocr Rev 1998, 19: 717–97.
Veldhuis JD, Johnson ML, Lizarralde G, Iranmanesh A. Rhythmic and non-rhythmic modes of anterior pituitary gland secretion: review of a model in which 24 hour rhythms in plasma concentrations of adenohypophysea hormones are generated by distinct amplitude and/or frequency modulation of underlying pituitary secretory bursts. In: Touitou Y, Haus E eds. Chronobiology international. Berlin: Springer Verlag 1992, 371–9.
Evans WS, Sollenberger MJ, Booth RA Jr, et al. Contemporary aspects of discrete peak-detection algorithms. II. The paradigm of the luteinizing hormone pulse signal in women. Endocr Rev 1992, 13: 81–104.
Farhy LS, Straume M, Johnson ML, Kovatchev BP, Veldhuis JD. A construct of interactive feedback control of the GH axis in the male. Am J Physiol Regul Integr Comp Physio 2001, 281: R38–51.
Farhy LM, Straume M, Johnson MJ, Kovatchev B, Veldhuis JD. Unequal autonegative feedback by GH models the sexual dimorphism in GH secretory dynamics. Am J Physiol Regul Integr Comp Physiol 2002, 282: R753–64.
Straume M, Veldhuis JD, Johnson ML. Realistic emulation of highly irregular temporal patterns of hormone release: a computer-based pulse simulator. Methods Neurosci 1995, 28: 220–43.
Straume M, Chen L, Johnson ML, Veldhuis JD. Systems-level analysis of physiological regulation interactions controlling complex secretory dynamics of growth hormone axis: a connectionist network model. Methods Neurosci 1995, 28: 270–310.
Veldhuis JD. Issues in quantifying pulsatile neurohormone release. In: van de Kar LD ed. Methods in neuroen-docrinology: the cellular and molecular neuropharmacology series. Boca Raton: CRC Press 1998, 181–203.
Mauras N, Rogol AD, Haymond MW, Veldhuis JD. Sex steroids, growth hormone, insulin-like growth factor-1: neuroendocrine and metabolic regulation in puberty. Horm Res 1996, 45: 74–80.
Keenan DM, Veldhuis JD. A biomathematical model of time-delayed feedback in the human male hypothalamic-pituitary-Leydig cell axis. Am J Physiol 1998, 275: E157–76.
Keenan DM, Licinio J, Veldhuis JD. A feedback-controlled ensemble model of the stress-responsive hypothalamo-pi-tuitary-adrenal axis. Proc Natl Acad Sci USA 2001, 98: 4028–33.
Hartman ML, Faria AC, Vance ML, Johnson ML, Thorner MO, Veldhuis JD. Temporal structure of in vivo growth hormone secretory events in man. Am J Physiol 1991, 260: E101–10.
Holl RW, Hartman ML, Veldhuis JD, Taylor WM, Thorner MO. Thirty-second sampling of plasma growth hormone in man: correlation with sleep stages. J Clin Endocrino Metab 1991, 72: 854–61.
Martha PM Jr, Goorman KM, Blizzard RM, Rogol AD, Veldhuis JD. Endogenous growth hormone secretion and clearance rates in normal boys, as determined by decon-volution analysis: relationship to age, pubertal status, and body mass. J Clin Endocrinol Metab 1992, 74: 336–44.
van den Berg G, Veldhuis JD, Frolich M, Roelfsema F. An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women. J Clin Endocrinol Metab 1996, 81: 2460–7.
Veldhuis JD, Roemmich JN, Rogol AD. Gender and sexual maturation-dependent contrasts in the neuroregulation of growth-hormone (GH) secretion in prepubertal and late adolescent males and females — a general clinical research center-based study. J Clin Endocrinol Metab 2000, 85: 2385–94.
Shah N, Evans WS, Veldhuis JD. Actions of estrogen on the pulsatile, nyctohemeral, and entropic modes of growth hormone secretion. Am J Physiol 1999, 276: R1351–8.
Gentili A, Mulligan T, Godschalk M, et al. Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. J Clin Endocrinol Metab 2002, 87: 825–34.
Hartman ML, Veldhuis JD, Johnson ML, et al. Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a 2-day fast in normal men. J Clin Endocrino Metab 1992, 74: 757–65.
Veldhuis JD, Carlson ML, Johnson ML. The pituitary gland secretes in bursts: appraising the nature of glandular secretory impulses by simultaneous multiple-parameter de-convolution of plasma hormone concentrations. Proc Natl Acad Sci (USA) 1987, 84: 7686–90.
Veldhuis JD, Johnson ML. Specific methodological approaches to selected contemporary issues in deconvolu-tion analysis of pulsatile neuroendocrine data. Meth Neurosci 1995, 28: 25–92.
de Zegher F, Devlieger H, Eggermont E, Veldhuis JD. Properties of growth hormone and prolactin hypersecretion by the human infant on the day of birth. J Clin Endocrinol Metab 1993, 76: 1177–81.
de Zegher F, Van den Berghe G, Devlieger H, Eggermont E, Veldhuis JD. Dopamine inhibits growth hormone and prolactin secretion in the human newborn. Pediatr Res 1993, 34: 642–5.
Veldhuis JD, Metzger DL, Martha Jr. PM, et al. Estrogen and testosterone, but not a non-aromatizable androgen, direct network integration of the hypothalamo-soma-totrope (growth hormone)-insulin-like growth factor I axis in the human: evidence from pubertal pathophysiology and sex-steroid hormone replacement. J Clin Endocrino Metab 1997, 82: 3414–20.
Iranmanesh A, Grisso B, Veldhuis JD. Low basal and persistent pulsatile growth hormone secretion are revealed in normal and hyposomatotropic men studied with a new ultrasensitive chemiluminescence assay. J Clin Endocrino Metab 1994, 78: 526–35.
Veldhuis JD, Liem AY, South S, et al. Differential impact of age, sex-steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 1995, 80: 3209–22.
Richmond E, Rogol AD, Basdemir D, et al. Accelerated escape from GH autonegative feedback in midpuberty in males: evidence for time-delimited GH-induced somato-statinergic outflow in adolescent boys. J Clin Endocrinol Metab 2002, 87: 3837–44.
Mauras N, Blizzard RM, Link K, Johnson ML, Rogol AD, Veldhuis JD. Augmentation of growth hormone secretion during puberty: Evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab 1987, 64: 596–601.
Weltman A, Weltman JY, Schurrer R, Evans WS, Veldhuis JD, Rogol AD. Endurance training amplifies the pulsatile release of growth hormone: effects of training intensity. J Appl Physiol 1992, 76: 2188–96.
Ulloa-Aguirre A, Blizzard RM, Garcia-Rubi E, et al. Testosterone and oxandrolone, a non-aromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life. J Clin Endocrinol Metab 1990, 71: 846–54.
Giustina A, Scalvini T, Tassi C, et al. Maturation of the regulation of growth hormone secretion in young males with hypogonadotropic hypogonadism pharmacologically exposed to progressive increments in serum testosterone. J Clin Endocrinol Metab 1997, 82: 1210–9.
Veldhuis JD, Evans WS, Bowers CY, Anderson S. Interactive regulation of the postmenopausal growth hormone insulin-ike growth factor axis by estrogen and growth hormone-releasing peptide-2. Endocrine 2001, 14: 45–62.
Veldhuis JD, Evans WS, Shah N, Story S, Bray MJ, Anderson SM. Proposed mechanisms of sex-steroid hormone neuromodulation of the human GH-IGF-I axis. In: Veldhuis JD, Giustina A eds. Sex-steroid interactions with growth hormone. New York: Springer-Verlag New York, nc. 1999, 93–121.
Fryburg DA, Weltman A, Jahn LA, et al. Androgenic modulation of the growth hormone-IGF axis and its impact on metabolic outcomes. In: Veldhuis JD, Giustina A eds. Sex-steroid interaction with growth hormone. New York: Springer-Verlag New York, Inc. 1999, 82–92.
Veldhuis JD, Bidlingmaier M, Anderson SM, Wu Z, Strasburger CJ. Lowering total plasma IGF-I concentrations by way of a novel, potent and selective GH-receptor antagonist, pegvisomant (B2036-PEG), augments the amplitude of GH secretory bursts and elevates basal/nonpul-satile GH release in healthy women and men. J Clin Endocrinol Metab 2001, 86: 3304–10.
Van den Berghe G, Wouters P, Weekers F, et al. Reactivation of pituitary hormone release and metabolic improvement by infusion of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness. J Clin Endocrinol Metab 1999, 84: 1311–23.
Evans WS, Anderson SM, Hull LT, Azimi PP, Bowers CY, Veldhuis JD. Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1,44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states. J Clin Endocrinol Metab 2001, 86: 700–12.
Veldhuis JD, Evans WS, Bowers CY. Impact of estradio supplementation on dual peptidyl drive of growth-hormone secretion in postmenopausal women. J Clin Endocrinol Metab 2002, 87: 859–66.
Iranmanesh A, South S, Liem AY, et al. Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotropic, IGF-I, and IGF-binding protein responses to a 3-day intravenous growth-hormonereleasing-hormone (GHRH) pulsatile infusion. Eur J Endocrinol 1998, 139: 59–71.
Anderson SM, Shah N, Patrie JT, Evans WS, Bowers CY, Veldhuis JD. Short-term estradiol supplementation augments growth hormone (GH)-secretory responsiveness to dose-varying growth hormone-releasing peptide (GHRP-2) infusions in postmenopausal women. J Clin Endocrinol Metab 2000, 86: 551–60.
Schaefer F, Baumann G, Faunt LM, et al. Multifactorial control of the elimination kinetics of unbound (free) GH in the human: regulation by age, adiposity, renal function, and steady-state concentrations of GH in plasma. J Clin Endocrinol Metab 1996, 81: 22–31.
Langendonk JG, Pijl H, Schoemaker R, et al. Estimates of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach. Am J Physio 2001, 280: R225–32.
Shah N, Aloi J, Evans WS, Veldhuis JD. Time-mode of growth hormone (GH) entry into the bloodstream and steady-state plasma GH concentrations rather than sex, estradiol, or menstrual-cycle stage primarily determine the GH elimination rate in healthy young women and men. J Clin Endocrinol Metab 1999, 84: 2862–9.
Ovesen P, Vahl N, Christiansen JS, Veldhuis JD, Jorgensen JO. Menstrual cycle interaction with the growth hormone axis. In: Veldhuis JD, Giustina A eds. Sex-steroid interactions with growth hormone. New York: Springer-Verlag New York, Inc. 1999, 67–73.
Anderson SM, Wideman L, Patrie JT, Weltman A, Bowers CY, Veldhuis JD. Estradiol supplementation selectively reieves growth hormone (GH)’s autonegative feedback on GH-releasing peptide-2 (GHRP-2)-stimulated GH secretion. J Clin Endocrinol Metab 2002, 86: 5904–11.
Veldhuis JD, Lassiter AB, Johnson ML. Operating behavior of dual or multiple endocrine pulse generators. Am J Physiol 1990, 259: E351–E61.
Vahl N, Jorgensen JO, Skjaerback C, Veldhuis JD, Orskov H, Christiansen J. Abdominal adiposity rather than age and sex predicts the mass and patterned regularity of growth hormone secretion in mid-life healthy adults. Am J Physio 1997, 272: E1108–E16.
Pijl H, Langendonk JG, Burggraaf J, et al. Altered neu-roregulation of GH secretion in viscerally obese premenopausal women. J Clin Endocrinol Metab 2001, 86: 5509–15.
Veldhuis JD, Johnson ML, Faunt LM, Mercado M, Baumann G. Influence of the high-affinity growth hormone (GH)-binding protein on plasma profiles of free and bound GH and on the apparent half-life of GH. J Clin Invest 1993, 91: 629–41.
Veldhuis JD, Faunt LM, Johnson ML. Analysis of nonequilibrium dynamics of bound, free, and total plasma ligand concentrations over time following nonlinear secretory inputs: evaluation of the kinetics of 2 or more hormones pulsed into compartments containing multiple variable-affinity binding proteins. Methods Enzymo 1994, 240: 349–77.
Veldhuis JD, Bidlingmaier M, Anderson SM, Evans WS, Wu Z, Strasburger CJ. Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men. J Clin Endocrinol Metab 2002, 87: 5737–45.
Johnson ML, Veldhuis JD. Evolution of deconvolution analysis as a hormone pulse detection method. Methods Neurosci 1995, 28: 1–24.
Veldhuis JD, Johnson ML. Deconvolution analysis of hormone data. Methods Enzymol 1992, 210: 539–75.
Urban RJ, Veldhuis JD. Hypothalamo-pituitary concomitants of aging. In: Sowers JR, Felicetta JV eds. The endocrinology of aging. New York: Raven Press 1988, 41–74.
Veldhuis JD, Fletcher TP, Gatford KL, Egan AR, Clarke IJ. Hypophyseal-portal somatostatin (SRIH) and jugular venous growth hormone secretion in the conscious unrestrained ewe. Neuroendocrinology 2002, 75: 83–91.
Keenan DM, Sun W, Veldhuis JD. A stochastic biomathematical model of the male reproductive hormone system. SIAM J of Appl Math 2000, 61: 934–65.
Keenan DM, Veldhuis JD. Stochastic model of admixed basal and pulsatile hormone secretion as modulated by a deterministic oscillator. Am J Physiol 1997, 273: R1182–92.
Veldhuis JD, Evans WS, Johnson ML. Complicating effects of highly correlated model variables on nonlinear least-squares estimates of unique parameter values and their statistical confidence intervals: estimating basal secretion and neurohormone half-life by deconvolution analysis. Methods Neurosci 1995, 28: 130–8.
Hartman ML, Pincus SM, Johnson ML, et al. Enhanced basal and disorderly growth hormone secretion distinguish acromegalic from normal pulsatile growth hormone re-ease. J Clin Invest 1994, 94: 1277–88.
Veldhuis JD, Pincus SM. Orderliness of hormone release patterns: a complementary measure to conventional pulsatile and circadian analyses. Eur J Endocrinol 1998, 138: 358–62.
Pincus SM, Hartman ML, Roelfsema F, Thorner MO, Veldhuis JD. Hormone pulsatility discrimination via coarse and short time sampling. Am J Physiol 1999, 277: E948–57.
Keenan DM, Veldhuis JD. Hypothesis testing of the aging male gonadal axis via a biomathematical construct. Am J Physiol Regul Integr Comp Physiol 2001, 280: R1755–71.
Pincus SM, Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis JD. Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males. Proc Natl Acad Sci USA 1996, 93: 14100–5.
Pincus SM. Approximate entropy as a measure of system complexity. Proc Natl Acad Sci USA 1991, 88: 2297–301.
Pincus SM, Keefe DL. Quantification of hormone pulsatility via an approximate entropy algorithm. Am J Physio 1992, 262: E741–54.
Veldhuis JD, Straume M, Iranmanesh A, et al. Secretory process regularity monitors neuroendocrine feedback and feedforward signaling strength in humans. Am J Physio Regul Integr Comp Physiol 2001, 280: R721–9.
van den Berg G, Pincus SM, Frolich M, Veldhuis JD, Roelfsema F. Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery. Eur J Endocrinol 1998, 138: 164–9.
van den Berg G, Pincus SM, Veldhuis JD, Frolich M, Roelfsema F. Greater disorderliness of ACTH and cortiso release accompanies pituitary-dependent Cushing’s Disease. Eur J Endocrinol 1997, 136: 394–400.
Roelfsema F, Pincus SM, Veldhuis JD. Patients with Cushing’s disease secrete adrenocorticotropin and cortisol jointly more asynchronously than healthy subjects. J Clin Endocrinol Metab 1998, 83: 688–92.
Veldman RG, van den Berg G, Pincus SM, Frolich M, Veldhuis JD, Roelfsema F. Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas. Eur J Endocrinol 1999, 140: 192–200.
Pincus SM, Gevers E, Robinson ICAF, et al. Females secrete growth hormone with more process irregularity than males in both human and rat. Am J Physiol 1996, 270: E107–15.
Pincus SM, Veldhuis JD, Rogol AD. Longitudinal changes in growth hormone secretory process irregularity assessed transpubertally in healthy boys. Am J Physiol Endocrinol Metab 2000, 279: E417–24.
Gevers E, Pincus SM, Robinson IC, Veldhuis JD. Differential orderliness of the GH release process in castrate male and female rats. Am J Physiol 1998, 274: R437–44.
Fryburg DA, Weltman A, Jahn LA, Weltman JY, Samolijik E, Veldhuis JD. Short-term modulation of the androgen milieu alters pulsatile but not exercise or GHRH-stimulat-ed GH secretion in healthy men. J Clin Endocrinol Metab 1997, 82: 3710–9.
Painson JC, Veldhuis JD, Tannenbaum GS. Single exposure to testosterone in adulthood rapidly induces regularity in the growth hormone release process. Am J Physio 2000, 278: E933–40.
Wu FCW, Butler GE, Kelnar CJH, Huhtaniemi I, Veldhuis JD. Patterns of pulsatile luteinizing hormone secretion from childhood to adulthood in the human male: a study using deconvolution analysis and an ultrasensitive immunofluorometric assay. J Clin Endocrinol Metab 1996, 81: 1798–805.
Veldhuis JD. Male hypothalamic-pituitary-gonadal axis. In: Yen SSC, Jaffe RB, Barbieri RL eds. Reproductive endocrinology. Philadelphia: WB Saunders Co 1999, 622–31.
Meneilly GS, Veldhuis JD, Elahi D. Disruption of the pulsatile and entropic modes of insulin release during an unvarying glucose stimulus in elderly individuals. J Clin Endocrinol Metab 1999, 84: 1938–43.
Veldhuis JD, Iranmanesh A, Mulligan T, Pincus SM. Disruption of the young-adult synchrony between luteinizing hormone release and oscillations in follicle-stimulating hormone, prolactin, and nocturnal penile tumescence (NPT) in healthy older men. J Clin Endocrinol Metab 1999, 84: 3498–505.
Veldhuis JD, Iranmanesh A, Godschalk M, Mulligan T. Older men manifest multifold synchrony disruption of reproductive neurohormone outflow. J Clin Endocrino Metab 2000, 85: 1477–86.
Mulligan T, Iranmanesh A, Kerzner R, Demers LW, Veldhuis JD. Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig-cell) defects in the healthy aging male gonadotropic axis. Eur J Endocrinol 1999, 141: 257–66.
Veldhuis JD, Iranmanesh A, Demers LM, Mulligan T. Joint basal and pulsatile hypersecretory mechanisms drive the monotropic follicle-stimulating hormone (FSH) elevation in healthy older men: concurrent preservation of the orderliness of the FSH release process. J Clin Endocrino Metab 1999, 84: 3506–14.
Pincus SM, Veldhuis JD, Mulligan T, Iranmanesh A, Evans WS. Effects of age on the irregularity of LH and FSH serum concentrations in women and men. Am J Physiol 1997, 273: E989–95.
Gravholt CH, Veldhuis JD, Christiansen JS. Increased disorderliness and decreased mass and daily rate of endogenous growth hormone secretion in adult Turner syndrome: the impact of body composition, maximal oxygen uptake and treatment with sex hormones. Growth Horm GF Res 1998, 8: 289–98.
Zwart A, Iranmanesh A, Veldhuis JD. Disparate serum free testosterone concentrations and degrees of hypothalamopituitary-LH suppression are achieved by continuous versus pulsatile intravenous androgen replacement in men: a clinical experimental model of ketoconazole-induced reversible hypoandrogenemia with controlled testosterone add-back. J Clin Endocrinol Metab 1997, 82: 2062–9.
Keenan DM, Veldhuis JD, Yang R. Joint recovery of pulsatile and basal hormone secretion by stochastic nonlinear random-effects analysis. Am J Physiol 1998, 274: R1939–49.
Veldhuis JD, Johnson ML, Veldhuis OL, Straume M, Pincus S. Impact of pulsatility on the ensemble orderliness (approximate entropy) of neurohormone secretion. Am J Physiol Regul Integr Comp Physiol 2001, 281: R1975–85.
Veldhuis JD, Zwart A, Mulligan T, Iranmanesh A. Muting of androgen negative feedback unveils impoverished go-nadotropin-releasing hormone/luteinizing hormone secretory reactivity in healthy older men. J Clin Endocrino Metab 2001, 86: 529–35.
Veldhuis JD, Iranmanesh A, Naftolowitz D, Tatham N, Cassidy F, Carroll BJ. Corticotropin secretory dynamics in humans under low glucocorticoid feedback. J Clin Endocrinol Metab 2001, 86: 5554–63.
Veldhuis JD. Neuroendocrine control of pulsatile growth-hormone release in the human: relationship with gender. Growth Horm IGF Res 1998, 8: 49–59.
Roelfsema F, Biermasz NR, Veldman RG, et al. Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile: evidence for a role for non-GHRH inputs into the generation of GH pulses. J Clin Endocrinol Metab 2000, 86: 2459–64.
Shuto Y, Shibasaki T, Otagiri A, et al. Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J Clin Invest 2002, 109: 1429–36.
Veldhuis JD, Iranmanesh A, Weltman A. Elements in the pathophysiology of diminished growth hormone (GH) secretion in aging humans. Endocrine 1997, 7: 41–8.
Mauras N, Rogol AD, Veldhuis JD. Increased hGH production rate after low-dose estrogen therapy in prepubertal girls with Turner’s syndrome. Pediatr Res 1990, 28: 626–30.
Veldhuis JD. Gender differences in secretory activity of the human somatotropic (growth hormone) axis. Eur J Endocrinol 1996, 134: 287–95.
Faria ACS, Bekenstein LW, Booth RA Jr, et al. Pulsatile growth hormone release in normal women during the menstrual cycle. Clin Endocrinol (Oxf) 1992, 36: 591–6.
Shah N, Evans WS, Bowers CY, Veldhuis JD. Oral estradiol administration modulates continuous intravenous growth hormone (GH)-releasing peptide-2 driven GH secretion in postmenopausal women. J Clin Endocrino Metab 2000, 85: 2649–59.
Bray MJ, Vick TM, Shah N, et al. Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin’s dose-dependent inhibition of fasting growth hormone secretion. J Clin Endocrinol Metab 2001, 86: 3143–9.
Evans WS, Bowers CY, Veldhuis JD. Estradiol supplementation enhances pituitary sensitivity to recombinant human (RH) GHRH-1, 44-amide in somatostatin (SS)-withdrawn postmenopausal women. Presented at the Endocrine Society 83rd Meeting, Denver, Colorado, June 20–23, 2001 (abstract).
Wideman L, Weltman JY, Anderson S, et al. A. Growth hormone (GH) autonegative feedback at rest and during exercise-stimulated GH release. First Joint Symposium GH-GF, Boston, MA, September 2002 (abstract).
Anderson SM, Kok P, Patrie JT, Veldhuis JD. Estrogen supplementation enhances rh IGF-I suppression of GH secretion in postmenopausal women. First Joint Symposium GH-IGF, Boston, MA, September 2002 (abstract).
Sites CK, Kessel B, LaBarbera AR. Adhesion proteins increase cellular attachment; follicle-stimulating hormone receptors, and progesterone production in cultured porcine granulosa cells. Proc Soc Exp Biol Med 1996, 212: 78–83.
Bellone J, Aimaretti G, Bartolotta E, et al. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, before and during puberty. J Clin Endocrinol Metab 1995, 80: 1090–4.
Ghigo E, Arvat E, Gianotti L, et al. Endocrine response to growth hormone-releasing peptides across human life span. In: Bercu BB, Walker RF eds. Growth hormone secretagogues in clinical practice. New York: Marcel Dekker nc 1998, 345–67.
Kaji H, Kishimoto M, Kirimura T, et al. Hormonal regulation of the human ghrelin receptor gene transcription. Biochem Biophys Res Commun 2001, 284: 660–6.
Kaji H, Tai S, Okimura Y, et al. Cloning and characterization of the 5′-flanking region of the human growth hormone secretagogue receptor gene. J Biol Chem 1998, 273: 33885–8.
Aguilar E, Tena-Sempere M, Pinilla L. 5-alpha androstanediol stimulates the pituitary growth hormone responsiveness to growth hormone releasing hormone more effectively than testosterone or dihydrotestosterone in rats. Acta Endocrinol (Copenh) 1992, 126: 162–6.
van den Berg G, Frolich M, Veldhuis JD, Roelfsema F. Growth hormone secretion in recently operated acromegalic patients. J Clin Endocrinol Metab 1994, 79: 1706–15.
Ovesen P, Vahl N, Fisker S, Veldhuis JD, Christiansen JS, Jorgensen JO. Increased pulsatile, but not basal, growth hormone secretion rates and plasma insulin-like growth factor I levels during the preovulatory interval in norma women. J Clin Endocrinol Metab 1998, 83: 1662–7.
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Veldhuis, J.D., Bowers, C.Y. Human GH pulsatility: An ensemble property regulated by age and gender. J Endocrinol Invest 26, 799–813 (2003). https://doi.org/10.1007/BF03345229
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DOI: https://doi.org/10.1007/BF03345229