Decreased Pulsatile Release of Growth Hormone in Old Male Rats*

Sonntag, William E.; Steger, Richard W.; Forman, Lloyd J.; Meites, Joseph

doi:10.1210/endo-107-6-1875

Cited by 282 publications

(138 citation statements)

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“…Although it is generally accepted that basal GH secretion decreases in humans and animals with increasing age (Borst et al, 1994;De Genarro Colonna et al, 1994;Finkelstein et al, 1972;Sonntag et al, 1980;Wilshire et al, 1995;Zadik et al, 1985), the basal plasma GH concentration in our study was not significantly different in the young and the old dogs. For identifying age-related differences in GH secretion, determination of the pulsatile secretion pattern of GH is much more sensitive.…”

Section: Ghrp-6contrasting

confidence: 75%

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Bhatti

Duchateau

Ham

et al. 2006

The Veterinary Journal

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The effects of three growth hormone secretagogues (GHSs), ghrelin, growth hormone-releasing peptide-6 (GHRP-6), and growth hormone-releasing hormone (GHRH), on the release of adenohypophyseal hormones, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinising hormone (LH), prolactin (PRL) and on cortisol were investigated in young and old healthy Beagle dogs.Ghrelin proved to be the most potent GHS in young dogs, whereas in old dogs GHRH administration was associated with the highest plasma GH concentrations. The mean plasma GH response after administration of ghrelin was significantly lower in the old dogs compared with the young dogs. The mean plasma GH concentration after GHRH and GHRP-6 administration was lower in the old dogs compared with the young dogs, but this difference did not reach statistical significance. In both age groups, the GHSs were specific for GH release as they did not cause significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH, and PRL. It is concluded that in young dogs, ghrelin is a more powerful stimulator of GH release than either GHRH or GHRP-6. Ageing is associated with a decrease in GH-releasing capacity of ghrelin, whereas this decline is considerably lower for GHRH or GHRP-6.

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Section: Ghrp-6contrasting

confidence: 75%

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Bhatti

Duchateau

Ham

et al. 2006

The Veterinary Journal

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“…In old male rats GH secretion is depressed, and this is associated with diminished pulsatile release of GH. The amplitude and duration of the pulses decrease, but the periodicity or number of pulses appears to be similar to that present in younger animals (9). That this decline in GH secretion of aging rats is due to aging and not to weight increase associated with aging was demonstrated in previous studies from our laboratory (10).…”

Section: Introductionmentioning

confidence: 50%

Sensitivity to exogenous GH and reversibility of the reduced IGF-I gene expression in aging rats

Velasco

Cacicedo

Melián

et al. 2001

European Journal of Endocrinology

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Background: IGF-I gene expression and IGF-I plasma concentration decline with age. A decreased sensitivity to GH has been suggested to be a contributory mechanism to this, in addition to attenuated GH secretion. Objective: This study focuses on the sensitivity to exogenous GH and the reversibility of the reduced IGF-I gene expression in aging male rats. Design: Three groups of male Wistar rats aged 3 months (young adult), 11 months (middle-aged) and 27 months (old), received recombinant human GH (rhGH) (150 mg/12 h s.c.) for seven consecutive days.Results: This rhGH treatment completely reversed plasma immunoreactive IGF-I (IR-IGF-I) and hepatic IGF-I mRNA levels in 11-month-old and 27-month-old animals to the levels of the young group of animals. The sensitivity in the old group (percentage of increment after the same or lower dose of rhGH per body weight) was increased for both parameters; serum IGF-I increment: 15% in 3-month-old, 42.6% in 11-month-old and 119.1% in 27-month-old rats; and hepatic IGF-Ib mRNA increase: 45% in 3-month-old, 27.8% in 11-month-old and 64.3% in 27-month-old rats. IGF binding protein-3 (IGFBP-3) mRNA level in the liver was significantly decreased in the old group and only a partial reversion occurred in this group after rhGH treatment; the percentage of increment was also higher in the old group of rats. In extrahepatic tissues IGF-I mRNA was not significantly different in the kidney and the testis of the three groups, and the rhGH treatment produced a significant and similar increase of IGF-I mRNA level in the kidney of the three groups of rats and in the testis of the 27-month-old animals. The GHr/GHBP mRNA remained unchanged in the liver and in the kidney or the testis of the three groups, and was not influenced by the rhGH treatment. Exogenous rhGH decreased pituitary GH mRNA accumulation in a more intense manner in the old group versus control of each group: young adult, 25%; middle-aged, 41.2%; and old rats, 55%. The action of rhGH on pituitary immunoreactive GH (IR-GH) content was only significantly evident in the young group. Conclusions: These results establish that exogenous rhGH recovers the attenuated liver IGF-I gene expression and the diminished plasma IR-IGF-I in old rats to the levels of young adult animals. They also indicate that the hepatic and extrahepatic (kidney and testis) sensitivity to one established dose per weight of exogenous rhGH is not altered in old animals, or could be potentially increased in some tissues.

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“…The mechanisms involved are unknown but may be due to alterations in the release of GRF and/or SRIF from the hypothalamus. For instance, a decrease in hypothalamic SRIF content has been noted in old rats (34). However, while injection of antiserum to SRIF in both young and old rats produces a similar increase of plasma GH in both age groups, a higher dose of antiserum causes an increase of plasma GH that is greater in the older than in the younger group (41).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have indicated that high-amplitude GH pulses in rats and humans, mean blood GH secretion in rats, and integrated GH values in humans diminish during aging (33)(34)(35)(36)(37)(38)(39)(40)(41). The mechanisms involved are unknown but may be due to alterations in the release of GRF and/or SRIF from the hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems.

Audhya¹,

Manzione²,

Nakane³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Polyclonal antibodies to synthetic human pancreatic growth hormone-releasing factor )NH2] and rat hypothalamic growth hormone-releasing factor [rhGRF(1-43)OHJ were produced in rabbits by injecting these weak immunogens, coupled to thyroglobulin and emulsified with complete Freund's adjuvant in the presence of activated charcoal, directly into the spleen. A subsequent booster in-jection by the conventional intramuscular route resulted in high-titer antibodies, which at a 1:20,000 dilution were used to develop highly sensitive and specific radioinmunoassays for these peptides. By using antibodies with an apparent K. of 3.3x 10-12 (human) and 7.7 x 10-11 (rat), the sensitivity of these assays in both human and rat was found to be <1 fmol. The antibody to hpGRF(1-44)NH2 is directed against the COOHterminal region of the molecule, as shown by its crossreactivity with various hpGRF analogues: 140% with hpGRF(30-44)NH2; 1%-2% with hpGRF(1-37)OH, hpGRF(140)OH, and hpGRF(1-40)NH2; and none with hpGRF(1-29)NH2. Serial dilutions of human and rat hypothalamic extracts demonstrated parallelism with the corresponding species-specific standard and 12,5-labeled tracer. There was no crossreactivity with other neuropeptides, gastrointestinal peptides, or hypothalamic extracts of other species. The hypothalamic content in fmol/mg (wet weight) of tissue was 3.6 ± 0.2 for the human and 11.1 ± 5.5 for the rat. Age-related changes in hypothalamic GRF content were present in rats, with a gradual increase from 2 to 16 weeks and a correlation between increasing body weight and GRF content. These radioimmunoassays winl serve as important tools for understanding the regulation of growth hormone secretion in both human and rat.Since 1959 (1), it has been known that the hypothalamus is involved in the control of growth hormone (GH) secretion. Experimental and clinical evidence has since indicated that the hypothalamus performs a dual function in the regulation of GH secretion from the anterior pituitary (2-4). Inhibition of GH release is accomplished by an inhibitory peptide, somatostatin (SRIF), which in 1972 was isolated from ovine hypothalami, purified, and characterized as a tetradecapeptide (5). In contrast, as suggested by physiological evidence (2-4) and GH-releasing activity in hypothalamic extracts (6-8), stimulation of GH release is accomplished by a stimulatory peptide, GH-releasing factor (GRF). Until 1982, howev-er, the isolation and characterization of GRF remained elusive. The difficulty in its characterization had been due to the minute quantities of the peptide in hypothalamic tissue, the large quantities of SRIF that interfere in the bioassay, and the fact that the methodology used for peptide sequencing and purification has only recently become available (9-12).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. 2970Many investigators have reported the presenc...

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Decreased Pulsatile Release of Growth Hormone in Old Male Rats*

Cited by 282 publications

References 0 publications

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Effects of growth hormone secretagogues on the release of adenohypophyseal hormones in young and old healthy dogs

Sensitivity to exogenous GH and reversibility of the reduced IGF-I gene expression in aging rats

Levels of human and rat hypothalamic growth hormone-releasing factor as determined by specific radioimmunoassay systems.

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