Antagonist to GH-releasing factor inhibits growth and renal Pi reabsorption in immature rats

1989 ◽  
Vol 257 (1) ◽  
pp. F29-F34 ◽  
Author(s):  
S. E. Mulroney ◽  
M. D. Lumpkin ◽  
A. Haramati
Keyword(s):  
Growth Hormone ◽  
Somatic Growth ◽  
Phosphate Transport ◽  
Adult Rats ◽  
Immature Rat ◽  
Pulsatile Release ◽  
Phosphate Reabsorption ◽  
Gh Secretion ◽  
Immature Rats ◽  
Male Wistar Rats

Compared with adult rats, the immature rat has an enhanced tubular capacity for phosphate reabsorption, which presumably facilitates the growth process. Since the main driving force for growth is thought to be the pulsatile release of growth hormone, we examined the possibility that the adaptation in phosphate handling by the immature kidney is promoted by growth hormone (GH). To address this issue, we used a synthetic peptide antagonist to GH-releasing factor (GRF-AN) that we have shown blocks episodic GH secretion, and attenuates somatic growth. Immature male Wistar rats (4–5 wk of age) were catheterized with Silastic jugular cannulas and placed in metabolic cages. The rats were injected intravenously with either saline or GRF-AN (100 micrograms/kg) twice daily for 4 days. On the 4th day, they were prepared for renal clearance experiments to assess the maximum capacity for phosphate transport (TmPi). In animals treated with GRF-AN, there was an attenuated gain in body weight over 4 days of treatment (5 +/- 2 vs. 23 +/- 2% in saline controls, P less than 0.01). The suppressed growth was associated with a doubling of daily urinary phosphate excretion, and a reduction in the TmPi (3.3 +/- 0.1 vs. 4.6 +/- 0.3 mumol/ml in controls, P less than 0.01). A single injection of the antagonist to a separate group of immature rats did not alter TmPi. Thus injections of this new antagonist to GH-releasing factor over a 4-day period inhibit the pulsatile release of GH and significantly attenuate growth. The decline in growth of the immature rat was associated with a decrease in the renal capacity for phosphate reabsorption, down to levels seen in normal adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of growth hormone release restores phosphaturic response to PTH in immature rats

1991 ◽  
Vol 261 (6) ◽  
pp. F1110-F1113 ◽  
Author(s):  
S. E. Mulroney ◽  
M. D. Lumpkin ◽  
A. Haramati
Keyword(s):  
Growth Hormone ◽  
Synthetic Peptide ◽  
Fractional Excretion ◽  
Hormone Release ◽  
Adult Rats ◽  
Immature Rat ◽  
Phosphate Retention ◽  
Immature Rats ◽  
Control Adult ◽  
Fractional Excretion Of Phosphate

Immature rats display a blunted rise in urinary phosphate but not adenosine 3',5'-cyclic monophosphate (cAMP) excretion in response to parathyroid hormone (PTH), perhaps as a consequence of the increased demand for phosphate during growth. Because a major driving force for growth is growth hormone (GH), and in view of the fact that GH has been shown to promote renal phosphate retention in the immature animal, it is possible that GH may attenuate the phosphaturic effect of PTH. The objective of this study was to determine whether suppression of pulsatile GH release, during administration of a synthetic peptide antagonist to GH-releasing factor, i.e., [N-acetyl-Tyr1-D-Arg2]-GRF-(1-29)-NH2 (GRF-AN), alters the renal response to increasing doses of PTH (1.5-15.0 micrograms.100 g-1.h-1) in the acutely thyroparathyroidectomized immature rat. Baseline fractional excretion of phosphate (FEPi), before administration of PTH, was negligible in all groups (less than 0.05%). Infusion of PTH resulted in an attenuated rise in FEPi in immature control rats compared with adult control rats (from 3.8 +/- 1.4% at lowest PTH dose to 16.7 +/- 3.1% at highest dose in immature rats vs. 21.1 +/- 3.5 to 31.9 +/- 4.4% in adult rats, P less than 0.05). In contrast, immature rats treated for 2 days with GRF-AN (100 micrograms/kg, twice daily) displayed an enhanced phosphaturic response (FEPi from 12.0 +/- 4.2 to 42.9 +/- 3.7%, P less than 0.05) compared with immature control rats, which was not different from that observed in control adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal tubular sites of increased phosphate transport and NaPi-2 expression in the juvenile rat

2001 ◽  
Vol 280 (5) ◽  
pp. R1524-R1533 ◽  
Author(s):  
Craig Woda ◽  
Susan E. Mulroney ◽  
Nabil Halaihel ◽  
Lijun Sun ◽  
Paul V. Wilson ◽  
...  
Keyword(s):  
Brush Border Membrane ◽  
Immunofluorescence Microscopy ◽  
Phosphate Transport ◽  
Adult Rats ◽  
Juvenile Rats ◽  
Juvenile Animal ◽  
Male Wistar Rats ◽  
Proximal Tubular ◽  
Renal Micropuncture ◽  
Renal Tubular

To determine the tubular sites and mechanisms involved in enhanced renal phosphate (Pi) reabsorption seen in the juvenile animal, renal micropuncture experiments were performed in acutely thyroparathyroidectomized adult (>14 wk old) and juvenile (4 wk old) male Wistar rats fed either a normal Pi diet (NPD, 0.6% Pi) or low Pi diet (0.07% Pi) for 2 days, in the presence and absence of parathyroid hormone (PTH). Pi reabsorption was greater in proximal convoluted (PCT) and straight tubules (PST) of the juvenile compared with adult rats fed NPD, whether or not PTH was present. These findings were consistent with a greater Piuptake in brush-border membrane (BBM) vesicles from both superficial (SC) and outer juxtamedullary (JMC) cortices of juvenile animals. Western blot analysis revealed a 2- and 1.8-fold higher amount of NaPi-2 protein in the SC and JMC, respectively, in juvenile rats. Immunofluorescence microscopy also indicated that NaPi-2 protein expression was present in the proximal tubule (PT) BBM to a greater extent in juvenile rats. Dietary Pi restriction in juvenile rats resulted in a significant increase in Pi reabsorption in the PCT and PST segments. NaPi-2 expression in the PT BBM was also increased, as was the expression of intracellular NaPi-2 protein. These studies indicate that Pi reabsorption in both the PCT and PST segments of the renal tubule contributes to the attenuated response to PTH in the normal juvenile animal. In addition, dietary Pi restriction in the juvenile rat upregulates BBM NaPi-2 expression, which is associated with a further increase in proximal tubular Pi reabsorption.

Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mechanism Of Action ◽  
Direct Action ◽  
Male Rats ◽  
Surgical Ablation ◽  
Adult Rats ◽  
Gh Secretion ◽  
Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

Renal adaptation to changes in dietary phosphate during development

1990 ◽  
Vol 258 (6) ◽  
pp. F1650-F1656 ◽  
Author(s):  
S. E. Mulroney ◽  
A. Haramati
Keyword(s):  
Glomerular Filtration Rate ◽  
Wistar Rats ◽  
Filtration Rate ◽  
Phosphate Transport ◽  
Adult Rats ◽  
Renal Handling ◽  
Immature Rats ◽  
Renal Adaptation ◽  
Dietary Phosphate ◽  
Elevated Rate

The present study tested the hypothesis that the influence of dietary phosphate (Pi) on the renal handling of Pi changes during development. We evaluated whether variations in the dietary Pi content would alter the tubular capacity of Pi reabsorption [Max RPi/glomerular filtration rate (GFR)] in immature rats, which have a relatively greater Max RPi/GFR compared with adult rats. Then we examined the response of immature and adult Pi-deprived rats to dietary Pi replenishment. Studies were performed in acutely thyroparathyroidectomized Wistar rats at three different stages of development: immature (3- to 4-wk old), young (6- to 7-wk old), and adult (12- to 13-wk old). Animals were fed either low (0.07%)-, normal (0.7%), or high (1.8%)-phosphate diet (LPD, NPD, and HPD, respectively) for 4 days and were then prepared for renal clearance experiments to determine the Max RPi/GFR. On all dietary regimens, the Max RPi/GFR was highest in immature rats and decreased progressively with age. When fed LPD, immature rats, with an already elevated rate of phosphate transport, displayed a remarkable 68 +/- 13% increase in the Max RPi/GFR (from 5.58 +/- 0.29 to 9.47 +/- 0.76 mumol/ml, P less than 0.01). This was significantly greater than the 38 +/- 3% increase observed in adult rats (from 3.50 +/- 0.18 to 4.81 +/- 0.09 mumol/ml). Conversely, in response to HPD, the decrease in the Max RPi/GFR was smallest in immature rats (-42 +/- 2%) compared with the decrement in either young (-54 +/- 3%) or adult (-61 +/- 6%) rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Postnatal development of growth hormone and prolactin cells in male and female rat pituitary. An immunocytochemical light and electron microscopic study.

1987 ◽  
Vol 35 (3) ◽  
pp. 335-341 ◽  
Author(s):  
G Smets ◽  
B Velkeniers ◽  
E Finne ◽  
A Baldys ◽  
W Gepts ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Types ◽  
Female Rats ◽  
Male Rats ◽  
Intermediate Lobe ◽  
Female Rat ◽  
Electron Microscopic ◽  
Adult Rats ◽  
Gh Cells ◽  
Immature Rats

Localization and ultrastructural maturation of prolactin (PRL) and growth hormone (GH) cells were studied in pituitaries from neonatal, immature (4-6 weeks old), and adult rats (2-3 months old) by light and electron microscopic immunocytochemistry. The distribution pattern of these cells did not change with age. Both cell types were concentrated laterodorsally, with PRL cells adjacent to the intermediate lobe and GH cells nearer the center of the pars distalis. Labeling density of the immunogold reaction was highest for both hormones in immature rats. In neonatal and immature rats, one PRL cell type with granules 200 nm in diameter was present. In adult rats, two types of PRL cells were present: one containing polymorphous granules measuring about 500 nm (prevalent in female rats), the other with spherical granules about 200 nm (prevalent in male rats). No changes were detected in GH cells during maturation.

A model of diffuse traumatic brain injury in the immature rat

1996 ◽  
Vol 85 (5) ◽  
pp. 877-884 ◽  
Author(s):  
P. David Adelson ◽  
Paul Robichaud ◽  
Ronald L. Hamilton ◽  
Patrick M. Kochanek
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mortality Rate ◽  
Ventilatory Support ◽  
Average Weight ◽  
Adult Rats ◽  
Immature Rat ◽  
Diffuse Brain Injury ◽  
Immature Rats ◽  
Severe Tbi

✓ Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague—Dawley immature rats (17 days old; average weight 38.5 ± 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 ± 0.23 minutes (mean ± standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 ± 3.99 minutes) and SI (20.57 ± 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 ± 1.0 g, 1.2 ± 1.6 g, and −0.6 ± 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 ± 0.7 minutes and 1.27 ± 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 ± 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.

Single exposure to testosterone in adulthood rapidly induces regularity in the growth hormone release process

2000 ◽  
Vol 278 (5) ◽  
pp. E933-E940 ◽  
Author(s):  
Jean-Claude Painson ◽  
Johannes D. Veldhuis ◽  
Gloria S. Tannenbaum
Keyword(s):  
Growth Hormone ◽  
Adult Life ◽  
Approximate Entropy ◽  
Female Rats ◽  
Female Rat ◽  
Adult Rats ◽  
Release Process ◽  
Intact Group ◽  
Gh Secretion ◽  
Plasma Gh

The neonatal gonadal steroid milieu is known to be important in imprinting the striking sexual dimorphism of growth hormone (GH) secretion; however, the influence of the sex steroids on GH control in adult life and their mechanism/site of action are largely unknown. In the present study, we tested the hypothesis that testosterone (T) subserves the gender-specific regularity of the GH release process in adulthood. The approximate entropy statistic (ApEn) was used to quantify the degree of regularity of GH release patterns over time. Eighteen hours after a single subcutaneous injection of 1 mg T, both sham-operated and ovariectomized (OVX) female adult rats displayed plasma GH profiles that were strikingly similar to the regular male-like ultradian rhythm of GH secretion. The highest ApEn values, denoting greater disorderliness of GH secretion, were observed in the ovary-intact group, and T injection significantly ( P < 0.001) reduced this irregularity whether or not the ovaries were present. Serial intravenous injections of GH-releasing hormone (GHRH) caused a similar increase in plasma GH levels in sham-operated females independently of time of administration. In contrast, female rats administered T exhibited a male-like intermittent pattern of GH responsiveness to GHRH, the latter known to be due to the cyclic release of endogenous somatostatin. These results demonstrate that acute exposure to T during adult life can rapidly and profoundly “masculinize” GH pulse-generating circuits in the female rat. Our findings suggest that the enhanced orderliness characteristic of the GH release process in males, compared with females, is regulated by T. We postulate that this T-induced regularity is mediated at the level of the hypothalamus by inducing regularity in somatostatin secretion, which in turn governs overall GH periodicity.

Genetic defects causing functional and structural isolated growth hormone deficiency

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Vibor Petkovic ◽  
Primus Mullis
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Somatic Growth ◽  
Human Growth ◽  
Postnatal Growth ◽  
Metabolic Effects ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Gh Secretion ◽  
Normal Standards

AbstractNormal somatic growth requires the integrated function of many of the hormonal, metabolic, and other growth factors involved in the hypothalamo-pituitary-somatotrope axis. Human growth hormone (hGH) causes a variety of physiological and metabolic effects in humans and its pivotal role in postnatal growth is undisputed. Disturbances that occur during this process often cause subnormal GH secretion and/or subnormal GH sensitivity/responsiveness resulting in short stature. Despite the complexity of this linear growth process, the growth pattern of children, if evaluated in the context of normal standards, is rather predictable. Children presenting with short stature (i.e out of normal standards) are treated with daily injections of recombinant human GH (rhGH), which leads in almost all cases to an increase of height velocity. Although it is becoming more and more evident that many genes are involved in controlling the regulation of growth, the main aim of this review is to focus on the GH-1 gene, the various gene alterations and their important physiological and pathophysiological role in growth.

Pulsatile secretion of growth hormone and insulin in relation to feeding in rats

1987 ◽  
Vol 253 (5) ◽  
pp. R772-R778
Author(s):  
P. Even ◽  
J. Danguir ◽  
S. Nicolaidis ◽  
C. Rougeot ◽  
F. Dray
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Food Intake ◽  
Wistar Rats ◽  
Plasma Concentrations ◽  
Endocrine Activity ◽  
Blood Samples ◽  
Gh Secretion ◽  
Male Wistar Rats ◽  
Intracardiac Catheters

In unrestrained male Wistar rats chronically implanted with intracardiac catheters, blood samples were taken every 20 min throughout the 24 h of the diurnal cycle. Plasma concentrations of growth hormone (GH), insulin, and glucose were measured. The pattern of food intake was continuously monitored. The existence of 3-h pulsatile cycles of GH secretion was confirmed. In addition, short bursts of insulin secretion were observed in the middle of every second GH peak-to-peak interval. Food intake appeared to be enhanced during short periods that corresponded with GH release into the blood and was reduced during the GH peak-to-peak periods in which the bursts of insulin secretion were observed. From these observations this study draws a schematic relationship between the rhythmicity of the secretion of GH and insulin and the probability of occurrence of feeding. We speculate that the rhythmic endocrine activity may be causally related to feeding.

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