Synergy ofl-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender

2000 ◽  
Vol 279 (4) ◽  
pp. R1455-R1466 ◽  
Author(s):  
Laurie Wideman ◽  
Judy Y. Weltman ◽  
James T. Patrie ◽  
C. Y. Bowers ◽  
Niki Shah ◽  
...  

We test the hypotheses that 1) growth hormone (GH)-releasing peptide-2 (G) synergizes with l-arginine (A), a compound putatively achieving selective somatostatin withdrawal and 2) gender modulates this synergy on GH secretion. To these ends, 18 young healthy volunteers (9 men and 9 early follicular phase women) each received separate morning intravenous infusions of saline (S) or A (30 g over 30 min) or G (1 μg/kg) or both, in randomly assigned order. Blood was sampled at 10-min intervals for later chemiluminescence assay of serum GH concentrations. Analysis of covariance revealed that the preinjection (basal) serum GH concentrations significantly determined secretagogue responsiveness and that sex ( P = 0.02) and stimulus type ( P < 0.001) determined the slope of this relationship. Nested ANOVA applied to log-transformed measures of GH release showed that gender determines 1) basal rates of GH secretion, 2) the magnitude of the GH secretory response to A, 3) the rapidity of attaining the GH maximum, and 4) the magnitude or fold (but not absolute) elevation in GH secretion above preinjection basal, as driven by the combination of A and G. In contrast, the emergence of the G and A synergy is sex independent. We conclude that gender modulates key facets of basal and A/G-stimulated GH secretion in young adults.

1993 ◽  
Vol 128 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Maria N Moreira-Andrés ◽  
Francisco J Cañizo ◽  
Federico Hawkins

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.


2002 ◽  
Vol 283 (4) ◽  
pp. E702-E710 ◽  
Author(s):  
Ralf Nass ◽  
Suzan S. Pezzoli ◽  
Ian M. Chapman ◽  
James Patrie ◽  
Raymond L. Hintz ◽  
...  

Arginine stimulates growth hormone (GH) secretion, possibly by inhibiting hypothalamic somatostatin (SS) release. Insulin-like growth factor I (IGF-I) inhibits GH secretion via effects at the pituitary and/or hypothalamus. We hypothesized that if the dominant action of IGF-I is to suppress GH release at the level of the pituitary, then the arginine-induced net increase in GH concentration would be unaffected by an IGF-I infusion. Eight healthy young adults (3 women, 5 men) were studied on day 2 of a 47-h fast for 12 h (35th-47th h) on four occasions. Saline (Sal) or 10 μg · kg−1 · h−1recombinant human IGF-I was infused intravenously for 5 h from 37 to 42 h of the 47-h fast. Arginine (Arg) (30 g iv) or Sal was infused over 30 min during the IGF-I or Sal infusion from 40 to 40.5 h of the fast. Subjects received the following combinations of treatments in random order: 1) Sal + Sal; 2) Sal + Arg; 3) IGF-I + Sal; 4) IGF-I + Arg. Peak GH concentration on the IGF-I + Arg day was ∼45% of that on the Sal + Arg day. The effect of arginine on net GH release was calculated as [(Sal + Arg) − (Sal + Sal)] − [(IGF-I + Arg) − (IGF-I + Sal)]. There was no significant effect of IGF-I on net arginine-induced GH release over control conditions. These findings suggest that the negative feedback effect of IGF-I on GH secretion is primarily mediated at the pituitary level and/or at the hypothalamus through a mechanism different from the stimulatory effect of arginine.


2005 ◽  
Vol 90 (4) ◽  
pp. 2225-2232 ◽  
Author(s):  
Cacia Soares-Welch ◽  
Leon Farhy ◽  
Kristi L. Mielke ◽  
Farid H. Mahmud ◽  
John M. Miles ◽  
...  

Abstract The present study examines the thesis that pulsatile GH secretion is controlled simultaneously by three principal signals; viz., GHRH, GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS). According to this ensemble notion, no single regulatory peptide acts alone or can be interpreted in isolation. Therefore, to investigate gender-specific control of pulsatile GH secretion, we designed dual-effector stimulation paradigms in eight young men and six women as follows: 1) l-arginine/GHRH (to clamp low SS and high GHRH input); 2) l-arginine/GHRP-2 (to clamp low SS and high GHRP drive); 3) GHRH/GHRP-2 (to clamp high GHRH and high GHRP feedforward); vs. 4) saline (unclamped). Statistical comparisons revealed that: 1) fasting pulsatile GH secretion was 7.6-fold higher in women than men (P &lt; 0.001); 2) l-arginine/GHRH and l-arginine/GHRP-2 evoked, respectively, 4.6- and 2.2-fold greater burst-like GH release in women than men (P &lt; 0.001 and P = 0.015); and 3) GHRH/GHRP-2 elicited comparable GH secretion by gender. In the combined cohorts, estradiol concentrations positively predicted responses to l-arginine/GHRP-2 (r2 = 0.49, P = 0.005), whereas testosterone negatively predicted those to l-arginine/GHRH (r2 = 0.56, P = 0.002). Based upon a simplified biomathematical model of three-peptide control, the current outcomes suggest that women maintain greater GHRH potency, GHRP efficacy, and opposing SS outflow than men. This inference upholds recent clinical precedence and yields valid predictions of sex differences in self-renewable GH pulsatility.


1984 ◽  
Vol 106 (3) ◽  
pp. 393-399 ◽  
Author(s):  
Elio Roti ◽  
Giuseppe Robuschi ◽  
Alessandro Alboni ◽  
Rossella Emanuele ◽  
Lorenzo d' Amato ◽  
...  

Abstract. Somatostatin (SRIF) was infused (500 μg over 30 min) into 68 pregnant women during labour. As a control, saline was infused into 26 pregnant women. Maternal blood was obtained prior to the infusion and at delivery and cord blood was obtained at delivery. The subjects were divided into 4 groups based upon the interval of time from the termination of SRIF infusion and delivery. There was a marked decrease in cord blood thyrotrophin (TSH) from 0 to 180 min and in cord blood growth hormone (GH) from 0 to 120 min following SRIF infusion. SRIF infusion did not affect cord blood iodothyronine and thyroglobulin concentrations. SRIF administration induced a small but significant (P < 0.05) decrease in serum GH concentration but had no other effect on maternal hormone values. These studies strongly suggest that SRIF crosses the human placenta and transiently suppresses foetal anterior pituitary TSH and GH secretion.


1999 ◽  
Vol 87 (3) ◽  
pp. 1154-1162 ◽  
Author(s):  
Laurie Wideman ◽  
Judy Y. Weltman ◽  
Niki Shah ◽  
Shannon Story ◽  
Johannes D. Veldhuis ◽  
...  

We examined gender differences in growth hormone (GH) secretion during rest and exercise. Eighteen subjects (9 women and 9 men) were tested on two occasions each [resting condition (R) and exercise condition (Ex)]. Blood was sampled at 10-min intervals from 0600 to 1200 and was assayed for GH by chemiluminescence. At R, women had a 3.69-fold greater mean calculated mass of GH secreted per burst compared with men (5.4 ± 1.0 vs. 1.7 ± 0.4 μg/l, respectively) and higher basal (interpulse) GH secretion rates, which resulted in greater GH production rates and serum GH area under the curve (AUC; 1,107 ± 194 vs. 595 ± 146 μg ⋅ l−1⋅ min, women vs. men; P = 0.04). Compared with R, Ex resulted in greater mean mass of GH secreted per burst, greater mean GH secretory burst amplitude, and greater GH AUC (1,196 ± 211 vs. 506 ± 90 μg ⋅ l−1⋅ min, Ex vs. R, respectivley; P < 0.001). During Ex, women attained maximal serum GH concentrations significantly earlier than men (24 vs. 32 min after initiation of Ex, respectively; P = 0.004). Despite this temporal disparity, both genders had similar maximal serum GH concentrations. The change in AUC (adjusted for unequal baselines) was similar for men and women (593 ± 201 vs. 811 ± 268 μg ⋅ l−1⋅ min), but there were significant gender-by-condition interactive effects on GH secretory burst mass, pulsatile GH production rate, and maximal serum GH concentration. We conclude that, although women exhibit greater absolute GH secretion rates than men both at rest and during exercise, exercise evokes a similar incremental GH response in men and women. Thus the magnitude of the incremental secretory GH response is not gender dependent.


1976 ◽  
Vol 41 (4) ◽  
pp. 523-527 ◽  
Author(s):  
J. Sutton ◽  
L. Lazarus

This study was designed to compare the serum growth hormone (GH) response with quantified exercise to that obtained with other stimuli. In eight normal males, aged 21–24 yr, we studied the serum GH response to 20 min cycle ergometer exercise at 300, 600, and 900 kpm/min on three separate occasions and compared the results with those found during sleep, insulin hypoglycemia, arginine infusion, and L-DOPA. Exercise at 900 kpm/min and insulin hypoglycemia resulted in the greatest elevations in serum GH which weresignificantly greater than those found with sleep, arginine or L-DOPA. The 20-min exercise at 900 kpm/min represented 75–90% of the subjects' maximal oxygen uptake and is a suitable provocative test for GH secretion. As a screening test for pituitary GH reserve, exercise compares favorably with insulin hypoglycemia and is superior to sleep, arginine, and L-DOPA.


1993 ◽  
Vol 128 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Bálint Kacsóh ◽  
Judith S Opp (Meyers) ◽  
William R Crowley ◽  
Clark E Grosvenor

Separation of neonatal rats from their mothers decreases, while a subsequent period of suckling (nursing) increases, serum growth hormone (GH) levels in neonatal rats. Milk-borne (humoral) factors and neural factors inherent in mother-offspring interaction have been implicated in these phenomena. Conflicting reports have demonstrated the α2-adrenergic agonist clonidine to increase and to decrease serum GH levels in 10-day-old rats. The present experiments were aimed at testing whether an interaction between the α2-adrenergic system and the nursing-induced changes in GH secretion could account for the discrepancy. Rat pups were treated with clonidine (150 μg/kg) or the α2-adrenergic antagonist yohimbine (10 mg/kg), and the drug treatment was combined with separation of the mothers and nursing. Yohimbine did not affect serum GH levels in separated two-day-old pups (i.e. basal levels of the hormone), but prevented the nursing-induced increase in serum GH concentration. In two-day-old pups, clonidine had no effect on basal GH levels but, like yohimbine, prevented the increase in serum GH normally associated with nursing. Both yohimbine and clonidine prevented active sucking behavior, i.e. the pups did not search for and/or attach to the nipples of their mothers. Moreover, the pups treated with yohimbine and clonidine were cooler to the touch than the littermate controls. In eight-day-old pups, yohimbine prevented the nursing-induced increase in serum GH and decreased GH levels below the saline-injected, separated control. As in two-day-old pups, clonidine prevented the suckling-induced release of GH and failed to induce GH-release above that of saline-injected, separated pups. By day 10 postpartum. clonidine became capable of stimulating GH release, but only in separated male pups. The effects of CLO and nursing in male pups were not additive: either treatment alone was as effective as the combined treatment. In female rats CLO prevented the increase in serum GH levels in response to nursing. It is concluded that (1) the α2-adrenergic agents yohimbine and clonidine inhibit nursing-induced GH secretion in an indirect (perhaps hypothermia-related) manner not involving the well-established α2-adrenergic-GH releasing hormone pathway; (2) the α2-adrenergic system becomes fully functional in terms of stimulation of GH secretion between days 8 and 10; (3) the GH-releasing effects of the α2-adrenergic system are sexually dimorphic in 10-day-old rats.


2009 ◽  
Vol 297 (2) ◽  
pp. E367-E374 ◽  
Author(s):  
Johannes D. Veldhuis ◽  
Susan B. Hudson ◽  
Dana Erickson ◽  
Joy N. Bailey ◽  
George Ann Reynolds ◽  
...  

Growth hormone (GH) secretion is subject to complex regulation. How pre- and postmenopausal age (PRE, POST), estradiol (E2) availability, and abdominal visceral fat (AVF) jointly affect peptidyl-secretagogue drive of GH secretion is not known. To this end, healthy PRE ( n = 20) and POST ( n = 22) women underwent a low- vs. high-E2 clamp before receiving a continuous intravenous infusion of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP-2). According to analysis of covariance, PRE and POST women achieved age-independent hypo- and euestrogenemia under respective low- and high-E2 clamps. All four of age ( P < 0.001), E2 status ( P = 0.006), secretagogue type ( P < 0.001), and an age × peptide interaction ( P = 0.014) controlled pulsatile GH secretion. Independently of E2 status, POST women had lower GH responses to both GHRH ( P = 0.028) and GHRP-2 ( P < 0.001) than PRE women. Independently of age, GHRP-2 was more stimulatory than GHRH during low E2 ( P = 0.011) and high E2 ( P < 0.001). Stepwise forward-selection multivariate analysis revealed that computerized tomographic estimates of AVF explained 22% of the variability in GHRH action ( P = 0.002), whereas age and E2 together explained 60% of the variability in GHRP-2 drive ( P < 0.001). These data establish that age, estrogen status, and AVF are triple covariates of continuous peptide-secretagogue drive of pulsatile GH secretion in women. Each factor must be controlled for to allow valid comparisons of GH-axis activity.


1996 ◽  
Vol 134 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Giuseppe Fanciulli ◽  
Osvaldo Oliva ◽  
Paolo A Tomasi ◽  
Alessandra Pala ◽  
Alba Bertoncelli ◽  
...  

Fanciulli G, Oliva O, Tomasi PA. Pala A. Bertoncelli A, Dettori A, Delitala G. Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. Eur J Endocrinol 1996:134:73–6. ISSN 0804–4643 Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli: in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opioids induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline: (b) a met-enkephalin analog G-DAMME 250 μg IV as a bolus at time ′: (c) hGH 2 IU as an IV bolus at time −180′; (d) G-DAMME as above, preceded by hGH as above. In our study. G-DAMME stimulated GH secretion both basally (peak 17.9 ± 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 ± 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded. Giuseppe Delitala, Chair of Endocrinology, Viale S. Pietro 12, University of Sassari, 07100 Sassari. Italy


ABSTRACT:Background:The most common cause of acromegaly is excess of growth hormone (GH) secretion.Methods:We report a 42-year-old male patient, who had become acromegalic over the past 5 years. There were no visual changes or change in sexual function, no gynaecomastia or galactorrhoea. Both CT and MRI scans showed a large mass measuring 2.5 x 2.5 x 3.5 cm, originating from the sella turcica and extending into and totally filling up the sphenoid sinus with diffusely invasive features.Results:Basal serum GH level was within normal range, but insulin-like growth factor 1 (IGF-1) was elevated with slightly increased prolactin (PRL) and impaired GH secretory regulation as well. A pituitary adenoma was partially removed through transsphenoidal microsurgery. Pathology confirmed a mammo-somatotrophic adenoma but immunocytochemistry study of the tumour showed only positivity for PRL but not GH.Conclusions:When acromegaly occurs without GH level elevation, one should pay attention that: 1) IGF-1 might be the cause of the clinical feature of acromegaly; 2) The tumour might undergo morphological transformation; and 3) Hyperinsulinemia or GH receptor antibody formation could also be the cause of the acromegalic appearance.


Sign in / Sign up

Export Citation Format

Share Document