scholarly journals Rising maternal circulating GH during murine pregnancy suggests placental regulation

2017 ◽  
Vol 6 (4) ◽  
pp. 260-266 ◽  
Author(s):  
Kathryn L Gatford ◽  
Beverly S Muhlhausler ◽  
Lili Huang ◽  
Pamela Su-Lin Sim ◽  
Claire T Roberts ◽  
...  
Keyword(s):  
Approximate Entropy ◽  
Late Pregnancy ◽  
Pulse Frequency ◽  
Maternal Blood ◽  
Placental Development ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Maternal Adaptation ◽  
Pregnant Mice ◽  
Murine Pregnancy

Placenta-derived hormones including growth hormone (GH) in humans contribute to maternal adaptation to pregnancy, and intermittent maternal GH administration increases foetal growth in several species. Both patterns and abundance of circulating GH are important for its activity, but their changes during pregnancy have only been reported in humans and rats. The aim of the present study was to characterise circulating profiles and secretory characteristics of GH in non-pregnant female mice and throughout murine pregnancy. Circulating GH concentrations were measured in whole blood (2 μL) collected every 10 min for 6 h in non-pregnant diestrus female C57Bl/6J mice (n = 9), and pregnant females at day 8.5–9.5 (early pregnancy, n = 8), day 12.5–13.5 (mid-pregnancy, n = 7) and day 17.5 after mating (late pregnancy, n = 7). Kinetics and secretory patterns of GH secretion were determined by deconvolution analysis, while orderliness and regularity of serial GH concentrations were calculated by approximate entropy analysis. Circulating GH was pulsatile in all groups. Mean circulating GH and total and basal GH secretion rates increased markedly from early to mid-pregnancy, and then remained elevated. Pulse frequency and pulsatile GH secretion rate were similar between groups. The irregularity of GH pulses was higher in all pregnant groups than that in non-pregnant mice. Increased circulating GH in murine pregnancy is consistent with an important role for this hormone in maternal adaptation to pregnancy and placental development. The timing of increased basal secretion from mid-pregnancy, concurrent with the formation of the chorioallantoic placenta and initiation of maternal blood flow through it, suggests regulation of pituitary secretion by placenta-derived factors.

Abdominal adiposity rather than age and sex predicts mass and regularity of GH secretion in healthy adults

1997 ◽  
Vol 272 (6) ◽  
pp. E1108-E1116 ◽  
Author(s):  
N. Vahl ◽  
J. O. Jorgensen ◽  
C. Skjaerbaek ◽  
J. D. Veldhuis ◽  
H. Orskov ◽  
...  
Keyword(s):  
Linear Regression Analysis ◽  
Maximal Oxygen Consumption ◽  
Approximate Entropy ◽  
Multiple Linear Regression Analysis ◽  
Abdominal Fat ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Major Predictor ◽  
Underlying Mechanisms ◽  
Age Range

We tested the hypothesis that body composition is the major predictor of growth hormone (GH) secretion in nonobese adults. We measured lean and fat tissue distribution (computerized tomography and dual-energy X-ray absorptiometry scan) and physical fitness [maximal oxygen consumption (Vo2max)] in 42 healthy nonobese adults (22 women and 20 men, age range 27-59 yr, mean +/- SE body mass index = 24 +/- 0.5 kg/m2). Deconvolution analysis was used to estimate specific features of 24-h GH secretion and clearance. Approximate entropy was used to quantify the regularity of GH release. Older subjects exhibited decreased estimates of GH secretion compared with younger subjects. Females had higher estimates of GH secretion, a longer GH half-life, and displayed more irregularity in GH release than males. Mean 24-h serum GH concentrations correlated inversely with intra-abdominal fat and waist-to-hip ratio and positively with Vo2max. Multiple linear regression analysis revealed intra-abdominal fat as the dominant determinant of estimates of GH secretion. Vo2max was more important than sex and age in predicting GH secretion. We conclude that abdominal fat is the major determinant of GH secretion in healthy nonobese adults. Although the underlying mechanisms remain elusive, our findings extend the clinical implications of visceral adiposity to include hyposomatotropism.

scholarly journals Estradiol Supplementation in Postmenopausal Women Attenuates Suppression of Pulsatile Growth Hormone Secretion by Recombinant Human Insulin-like Growth Factor Type I

2008 ◽  
Vol 93 (11) ◽  
pp. 4471-4478 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Daniel M. Keenan ◽  
Joy N. Bailey ◽  
Adenborduin Adeniji ◽  
John M. Miles ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Negative Feedback ◽  
Academic Medical Center ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Approximate Entropy ◽  
Type I ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Igf I

Background: Why pulsatile GH secretion declines in estrogen-deficient postmenopausal individuals remains unknown. One possibility is that estrogen not only enhances stimulation by secretagogues but also attenuates negative feedback by systemic IGF-I. Site: The study took place at an academic medical center. Subjects: Subjects were healthy postmenopausal women (n = 25). Methods: The study included randomized assignment to estradiol (n = 13) or placebo (n = 12) administration for 16 d and randomly ordered administration of 0, 1.0, 1.5, and 2.0 mg/m2 recombinant human IGF-I sc on separate days fasting. Analysis: Deconvolution analysis of pulsatile and basal GH secretion and approximate entropy (pattern-regularity) analysis were done to quantify feedback effects of IGF-I. Outcomes: Recombinant human IGF-I injections increased mean and peak serum IGF-I concentrations dose dependently (P < 0.001) and suppressed mean GH concentrations (P < 0.001), pulsatile GH secretion (P = 0.001), and approximate entropy (P < 0.001). Decreased GH secretion was due to reduced secretory-burst mass (P = 0.005) and frequency (P < 0.001) but not basal GH release (P = 0.52). Estradiol supplementation lowered endogenous, but did not alter infused, IGF-I concentrations while elevating mean GH concentrations (P = 0.012) and stimulating pulsatile (P = 0.008) and basal (P < 0.001) GH secretion. Estrogen attenuated IGF-I’s inhibition of pulsatile GH secretion (P = 0.042) but was unable to restore physiological GH pulse frequency or normalize approximate entropy. Conclusion: Short-term estrogen replacement in postmenopausal women selectively mutes IGF-I-mediated feedback on pulsatile GH secretion. Disinhibition of negative feedback thus confers a novel mechanism by which estrogen may obviate hyposomatotropism.

scholarly journals GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood

2006 ◽  
Vol 155 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Johan Svensson ◽  
Gudmundur Johannsson ◽  
Ali Iranmanesh ◽  
Kerstin Albertsson-Wikland ◽  
Johannes D Veldhuis ◽  
...  
Keyword(s):  
Young Adults ◽  
Gh Deficiency ◽  
Adult Life ◽  
Approximate Entropy ◽  
Longitudinal Growth ◽  
Lower Percentage ◽  
Healthy Controls ◽  
Gh Treatment ◽  
Deconvolution Analysis ◽  
Gh Secretion

Objective: Some adolescents who discontinue GH treatment due to GH deficiency (GHD) and short stature in childhood do not have classical GHD at retesting in adult life. It is unknown whether there is a neuroendocrine disturbance in the spontaneous pattern of GH release in these patients. Design/patients/methods: Thirty-seven adolescents, who had received treatment with GH due to impaired longitudinal growth, were included. The adolescents were divided into two groups; one (GHD; n = 19) with classical GHD in adult life and another (GH sufficient (GHS); n = 18) without classical adult GHD. One year after GH discontinuation, 24-h GH profiles were performed with blood sampling every 30 min. Sixteen matched healthy controls were also studied. All blood samples were analysed using an ultrasensitive GH assay and then, approximate entropy (ApEn) and deconvolution analysis were performed. Results: The GHD group had higher mean ApEn level than the healthy controls (P < 0.05). As measured by deconvolution analysis, they had lower basal GH secretion (P < 0.01), increased number of GH peaks (P < 0.001), but lower burst mass (P < 0.001), lower percentage pulsatile GH secretion (P < 0.001) and lower total GH secretion (P < 0.001), compared with control subjects. Adolescents in the GHS group had a pattern of 24-h GH release similar to that in healthy controls. Conclusion: Young adults with childhood-onset severe GHD have a high-frequency, low-amplitude GH secretion with decreased orderliness. The adolescents without classical GHD in adult life maintain a pattern of spontaneous GH release that is not statistically different from that in the healthy controls.

scholarly journals Overtrained horses alter their resting pulsatile growth hormone secretion

2009 ◽  
Vol 297 (2) ◽  
pp. R403-R411 ◽  
Author(s):  
E. de Graaf-Roelfsema ◽  
P. P. Veldhuis ◽  
H. A. Keizer ◽  
M. M. E. van Ginneken ◽  
K. G. van Dam ◽  
...  
Keyword(s):  
Growth Hormone ◽  
High Speed ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Approximate Entropy ◽  
Underlying Mechanism ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Pulsatility Pattern ◽  
It Training

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.

scholarly journals Impact of two or three daily subcutaneous injections of hexarelin, a synthetic growth hormone (GH) secretagogue, on 24-h GH, prolactin, adrenocorticotropin and cortisol secretion in humans

2002 ◽  
pp. 310-318 ◽  
Author(s):  
M Maccario ◽  
JD Veldhuis ◽  
F Broglio ◽  
LD Vito ◽  
E Arvat ◽  
...  
Keyword(s):  
Approximate Entropy ◽  
Sampling Period ◽  
Significant Rise ◽  
Cortisol Secretion ◽  
Burst Frequency ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Igf I ◽  
Cortisol Release ◽  
The Impact

OBJECTIVE: To extend the insights on the action of GH secretagogues (GHS) on pituitary function, we studied the impact of intermittent daily s.c. administration of a peptidyl GHS, hexarelin (HEX), on 24-h GH, PRL, ACTH and cortisol release in healthy volunteers. DESIGN: We investigated the impact of two or three times daily s.c. administration of a short-acting peptidyl GHS, the hexapeptide HEX (1.5 microg/kg) on 24-h GH, PRL, ACTH and cortisol secretion (sampling every 20 min) in six normal young men. To monitor possible down-regulation, the effect of 1 microg/kg i.v. HEX at the end of each 24-h sampling period was studied. METHODS: Multi-parameter deconvolution analysis was used to quantitate pulsatile GH, PRL, ACTH and cortisol secretion and estimate the corresponding hormone half-lives. Complementary to deconvolution analysis, approximate entropy was used as a scale- and model-independent statistic to quantify the serial orderliness or pattern regularity of hormone measurements. RESULTS: Mean and integrated (24-h) serum GH concentrations were increased from baseline values to the same extent by two and three HEX injections. Both HEX schedules equally increased GH secretory burst mass (but not burst frequency), mean daily GH production rate, GH half-life and irregularity of GH release patterns. No change occurred in the secretion of IGF-I, PRL, ACTH and cortisol. Intravenous HEX at the end of each spontaneous 24-h profile induced a significant rise in GH, PRL, ACTH and cortisol. Prior HEX administration blunted the GH response, abolished that of ACTH and cortisol and did not modify the PRL increase. CONCLUSIONS: The study showed that two or three daily s.c. injections of HEX augmented 24-h GH secretion equally, amplifying selectively GH secretory pulse mass without altering lactotroph and corticotroph secretion. IGF-I levels were not modified by these 1-day HEX treatment schedules.

scholarly journals Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa: Indirect Evidence for Disruption of Feedback Regulation within the GH-Insulin-Like Growth Factor I Axis1

1999 ◽  
Vol 84 (6) ◽  
pp. 2056-2063 ◽  
Author(s):  
René K. Støving ◽  
Johannes D. Veldhuis ◽  
Allan Flyvbjerg ◽  
Jørgen Vinten ◽  
Jørgen Hangaard ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Indirect Evidence ◽  
Feedback Regulation ◽  
Approximate Entropy ◽  
Fold Increase ◽  
Metabolic Effects ◽  
Release Process ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Secretion Rates

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted at 20-min intervals in 8 nonfasting patients with AN [body mass index (BMI), 14.2 ± 0.8 kg/m2; mean ± sem) and in 11 age-matched healthy women (BMI, 20.3 ± 0.5 kg/m2). The deconvolution-estimated half-life of GH was not altered in the AN patients. The pituitary GH secretory burst frequency, burst mass, and burst duration were each significantly increased in women with AN compared to those in normal weight women. A 4-fold increase in daily pulsatile GH secretion was accompanied by a 20-fold increase in basal (nonpulsatile) GH secretion. There were significant negative correlations between BMI and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate. The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN. Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone.

Nocturnal growth hormone secretory dynamics are altered after resistance exercise: deconvolution analysis of 12-hour immunofunctional and immunoreactive isoforms

2006 ◽  
Vol 291 (6) ◽  
pp. R1749-R1755 ◽  
Author(s):  
Alexander P. Tuckow ◽  
Kevin R. Rarick ◽  
William J. Kraemer ◽  
James O. Marx ◽  
Wesley C. Hymer ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Resistance Exercise ◽  
Approximate Entropy ◽  
Exercise Protocol ◽  
Burst Frequency ◽  
Release Process ◽  
Secretory Rate ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Main Effect

To characterize the effects of daytime exercise on subsequent overnight growth hormone (GH) secretion and elimination dynamics, serum was sampled, and GH was measured every 10 min for 12 h (1800 to 0600) in a control (CON) condition and after a 50-set resistance exercise protocol (EX) from 1500 to 1700. GH was measured with a conventional immunoreactive (IR) and an immunofunctional (IF) assay, and values were analyzed via a multi-parameter deconvolution analysis. EX resulted in a higher overnight secretory burst frequency [CON: 7.6 (SD 2.4) < EX: 9.4 (2.2) bursts per 12 h, P = 0.005] but lower mean burst mass [CON: 9.2 (4.7) > EX: 6.0 (2.9) μg/l, P = 0.019] and secretory rate [CON: 0.68 (0.29) > EX: 0.48 (0.23) μg/l/min; P = 0.015; ANOVA main effect means presented]. Approximate entropy (ApEn) was greater after EX, indicating a less orderly GH release process than CON. The estimated half-life of IF GH was significantly lower than IR GH [IF: 15.3 (1.1) < IR 19.8 (1.6) min, P < 0.001] but similar between the CON and EX conditions (∼17 min). Despite the changes in secretory dynamics, 12-h mean and integrated GH concentrations were similar between conditions. The results suggest that although quantitatively similar total amounts of GH are secreted overnight in CON and EX conditions, resistance exercise alters the dynamics of secretion by attenuating burst mass and amplitude yet increasing burst frequency.

Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion

1999 ◽  
Vol 276 (5) ◽  
pp. R1351-R1358 ◽  
Author(s):  
N. Shah ◽  
W. S. Evans ◽  
J. D. Veldhuis
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Approximate Entropy ◽  
Thyroid Stimulating Hormone ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Specific Regulation ◽  
Stimulating Hormone

The neuroendocrine mechanisms by which estradiol drives growth hormone (GH) secretion in the human are poorly defined. Here we investigate estrogen’s specific regulation of the 24-h pulsatile, nyctohemeral, and entropic modes of GH secretion in healthy postmenopausal women. Volunteers ( n = 9) received randomly ordered placebo versus estradiol-17β (1 mg micronized steroid twice daily orally) treatment for 7–10 days and underwent blood sampling at 10-min intervals for 24 h to capture GH release profiles quantitated in a high-sensitivity chemiluminescence assay. Pulsatile GH secretion was appraised via deconvolution analysis, nyctohemeral GH rhythms by cosinor analysis, and the orderliness of GH release patterns via the approximate entropy statistic. Mean (±SE) 24-h serum GH concentrations approximately doubled on estrogen treatment (viz., from 0.31 ± 0.03 to 0.51 ± 0.07 μg/l; P = 0.033). Concomitantly, serum insulin-like growth factor-I (IGF-I), luteinizing hormone, and follicle-stimulating hormone concentrations fell, whereas thyroid-stimulating hormone and prolactin levels rose ( P < 0.01). The specific neuroendocrine action of estradiol included 1) a twofold amplified mass of GH secreted per burst, with no significant changes in basal GH release, half-life, pulse frequency, or duration; 2) an augmented amplitude and mesor of the 24-h rhythm in GH release, with no alteration in acrophase; and 3) greater disorderliness of GH release (higher approximate entropy). These distinctive and dynamic reactions to estrogen are consistent with partial withdrawal of IGF-I’s negative feedback and/or accentuated central drive to GH secretion.

scholarly journals Increased Pulsatility, Process Irregularity, and Nocturnal Trough Concentrations of Growth Hormone in Amenorrheic Compared to Eumenorrheic Athletes1

2001 ◽  
Vol 86 (3) ◽  
pp. 1013-1019
Author(s):  
Debra L. Waters ◽  
Clifford R. Qualls ◽  
Richard Dorin ◽  
Johannes D. Veldhuis ◽  
Richard N. Baumgartner
Keyword(s):  
Oxygen Consumption ◽  
Hospital Admissions ◽  
Maximal Oxygen Consumption ◽  
Exercise Bout ◽  
Approximate Entropy ◽  
Sampling Period ◽  
Igf Binding Proteins ◽  
Deconvolution Analysis ◽  
Gh Secretion ◽  
Igf I

Amenorrheic athletes exhibit a spectrum of neuroendocrine disturbances, including alterations in the GH-insulin-like growth factor I (IGF-I) axis. Whether these changes are due to exercise or amenorrhea is incompletely characterized. The present study investigates spontaneous (overnight) and exercise-stimulated GH secretion and associated IGF-binding proteins (IGFBPs) in amenorrheic (AA; n = 5), and eumenorrheic athletes ( n = 5) matched for age, percent body fat (dual energy x-ray absorptiometry), training history, and maximal oxygen consumption. Each volunteer participated in two hospital admissions consisting of a 50-min submaximal exercise bout (70% maximal oxygen consumption) and an 8-h nocturnal sampling period. Deconvolution analysis of serum GH concentration time series revealed increases in the half-life of GH (60%) and the number of secretory bursts (85%) as well as a decrease in their half-duration (50%) and the mass of GH secreted per pulse (300%) in the AA cohort. Time occupancy at elevated trough GH concentrations was significantly increased, and GH pulsatility (approximate entropy) was more irregular in the AA group. During exercise, AA exhibited a reversal of the normal relationship between IGF-I and GH, and a 4- to 5-fold blunting of stimulated peak and integrated GH secretion. Fasting levels of plasma IGF-I, IGFBP-3, and IGFBP-1 appeared to be unaffected by menstrual status. In ensemble, this phenotype of GH release in amenorrheic athletes suggests disrupted neuroregulation of episodic GH secretion, possibly reflecting decreased somatostinergic inhibition basally, and reduced GHRH output in response to exercise compared with eumenorrheic athletes. Accordingly, we postulate that the amenorrheic state, beyond the exercise experience per se, alters the neuroendocrine control of GH output in amenorrheic athletes.

Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance

2002 ◽  
Vol 282 (4) ◽  
pp. E943-E951 ◽  
Author(s):  
Hiralal G. Maheshwari ◽  
Suzan S. Pezzoli ◽  
Asad Rahim ◽  
Stephen M. Shalet ◽  
Michael O. Thorner ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Approximate Entropy ◽  
Pulse Frequency ◽  
R Gene ◽  
Hormone Resistance ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Ghrh Receptor

Growth hormone (GH) secretion is regulated by GH-releasing hormone (GHRH), somatostatin, and possibly ghrelin, but uncertainty remains about the relative contributions of these hypophysiotropic factors to GH pulsatility. Patients with genetic GHRH receptor (GHRH-R) deficiency present an opportunity to examine GH secretory dynamics in the selective absence of GHRH input. We studied circadian GH profiles in four young men homozygous for a null mutation in the GHRH-R gene by use of an ultrasensitive GH assay. Residual GH secretion was pulsatile, with normal pulse frequency, but severely reduced amplitude (<1% normal) and greater than normal process disorder (as assessed by approximate entropy). Nocturnal GH secretion, both basal and pulsatile, was enhanced compared with daytime. We conclude that rhythmic GH secretion persists in an amplitude-miniaturized version in the absence of a GHRH-R signal. The nocturnal enhancement of GH secretion is likely mediated by decreased somatostatin tone. Pulsatility of residual GH secretion may be caused by oscillations in somatostatin and/or ghrelin; it may also reflect intrinsic oscillations in somatotropes.

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