Age-Related Changes in Growth Hormone Releasing Factor and Somatostatin in the Rat Hypothalamus

Morimoto, Nobumitsu; Kawakami, Fumio; Makino, Seiya; Chihara, Kazuo; Hasegawa, Miki; Ibata, Yasuhibo

doi:10.1159/000124950

Cited by 83 publications

(39 citation statements)

References 21 publications

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“…Age-related changes in these hormone secretions may alter the G H and PRL secretions through the gene expressions. Recently, diminished GHRH secretion, reduced responsiveness to GHRH and enhanced somatostatin release were observed (Sonntag et al, 1983(Sonntag et al, , 1986Morimoto et al, 1988). Functional decline in dopamine (PRL-inhibiting factor, PIF) neurons was also reported in several studies (Simpkins et al, 1977;Gudelsky et al, 1981).…”

Section: Discussionmentioning

confidence: 91%

Age-Related Changes in Growth Hormone and Prolactin Messenger RNA Levels in the Rat.

Takahashi¹,

Kawashima

Seo³

et al. 1990

Endocrinol Japon

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Section: Discussionmentioning

confidence: 91%

Age-Related Changes in Growth Hormone and Prolactin Messenger RNA Levels in the Rat.

Takahashi¹,

Kawashima

Seo³

et al. 1990

Endocrinol Japon

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“…In aged mammals, decreased responsiveness to GHRH and reduced GH plasma levels [5, 6, 7, 8] are thought to be responsible for a diminution of muscle mass, an increase of the adipose tissue mass and a deterioration of several tissue and organ functions [8, 9, 10, 11]. In 24-month-old rats, it has been partly related to a decrease in both GHRH hypothalamic content [12, 13] and gene expression [13], but not to a loss of GHRH-containing neurons [12]. The contribution of hypothalamic SRIF to a decreased GH secretion remains however a matter of debate [5, 6, 7, 12, 14, 15, 16, 17].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Calorie Restriction Protects Rat Pituitary Growth Hormone-Releasing Hormone Binding Sites from Age-Related Alterations

et al. 1998

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In mammals, middle age and late adulthood is characterized by a decrease of growth hormone (GH) secretion and insulin-like growth factor 1 (IGF-1) serum levels, contributing to tissue and organ atrophy. This condition is related, at least in part, to alterations of pituitary GH-releasing hormone (GHRH) receptor-binding sites. Prevention of age-related deterioration of tissues and organs, retardation of the onset or progression of a wide range of age-related diseases and extension of both mean and maximum life span can be achieved through life-long moderate calorie restriction (CR). Because CR has been reported to positively modulate the somatotropic axis resulting in the maintenance of a youthful GH secretory pattern in aged rats, we investigated whether or not benefits of a long-term (10 months) 40% CR, started in 8-month-old male Sprague-Dawley rats, was accomplished by preventing age-related alterations of pituitary GHRH receptor binding sites. We also studied whether or not a short-term (50 days) 40% CR, started in 16-month-old rats, could revert them. Potential hormonal and metabolic modulators of the GHRH receptors were investigated as well. GHRH binding parameters were derived from saturation studies performed in pituitary homogenates with [¹²⁵I-Tyr¹⁰]hGHRH (1-44)NH₂. As previously reported, the high affinity GHRH receptor-binding sites were blunted in 18-month-old ad libitum-fed rats and the apparent concentration of total binding sites was reduced. Short-term CR neither restored high affinity GHRH binding sites nor increased the apparent concentration of total binding sites. On the contrary, long-term calorie-restricted 18-month-old rats exhibited high and low affinity GHRH binding sites (K_d1: 1.73 ± 0.35 nM; K_d2: 310 ± 41 nM; B_max1: 183 ± 55 fmol/mg protein; B_max2: 30 ± 3 pmol/mg protein) as found in 2-month-old rats (K_d1: 0.68 ± 0.15 nM; K_d2: 350 ± 47 nM; B_max1: 219 ± 53 fmol/mg protein; B_max2: 84 ± 9 pmol/mg protein). Our results imply that CR must be implemented before age-related alterations of GHRH receptor-binding sites become too severe or that CR has to be carried out for a long period of time, independently from the age at which it begins. Protection of pituitary GHRH binding sites from age-related alterations could not be attributed to changes in circulating levels of total or free T₄ or free fatty acids. Finally, the anti-aging effect of a long-term CR observed at the level of pituitary GHRH receptors does not result in a significant increase of total IGF-1 circulating levels. Identification of molecular and cellular mechanisms responsible for these actions will deserve attention in order to identify centrally and/or peripherally active classes of molecules that could preserve, in aging mammals, the functionality of the somatotropic axis through selective regulation of pituitary GHRH receptors.

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“…Of these, GHRH plays a significant role in stimulating the production of somatotropes (21,22). The synthesis and secretion of GHRH in the hypothalamus is thought to be reduced in aged rats fed ad libitum (23,24). There is no direct evidence that GHRH is secreted in aged DR animals in a fashion similar to that observed in young counterparts fed ad libitum However, a recent study reported that pulsatile secretion of GH similar to that in young AL rats is present in aged DR rats, but not in aged AL rats (25), suggesting that GHRH is secreted efficiently in DR rats in later life.…”

Section: Discussionmentioning

confidence: 99%

Dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats

Shimokawa

Tomita

Higami

et al. 1997

AGE

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We investigated the impact of dietary restriction on the basal rate of somatotrope renewal in the pituitary gland. Bromodeoxyuridine (BrdU), a thymidine analog, was administered continuously for 1 week in male F344 rats at 3, 8 and 20 months of age (mo), fed ad libitum (AL) or diet restricted from 1.5 mo (DR). Combined immunostainings for BrdU and GH visualized newly formed somatotropes as well as pituitary cells in tissue sections. The rate of incorporation of BrdU by anterior pituitary cells (BrdUlabeled nuclei/100 nuclei) was not influenced by the dietary regimen or age. The fraction of BrdU-labeled somatotropes relative to all labeled cells precipitously decreased to the same level in both dietary groups between 3 and 8 mo, although the fraction was greater in DR rats at 3 too. In AL rats, the fraction decreased further between 8 and 20 mo, while it stabilized in DR rats. Our results suggested that dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats. Although one must also estimate the effects of dietary restriction on apoptotic cell death in pituitary cells, the present study provides evidence that dietary restriction modulates somatotropes cell turnover and preserves the cell population for GH secretion during aging.

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Age-Related Changes in Growth Hormone Releasing Factor and Somatostatin in the Rat Hypothalamus

Cited by 83 publications

References 21 publications

Age-Related Changes in Growth Hormone and Prolactin Messenger RNA Levels in the Rat.

Age-Related Changes in Growth Hormone and Prolactin Messenger RNA Levels in the Rat.

Long-Term Calorie Restriction Protects Rat Pituitary Growth Hormone-Releasing Hormone Binding Sites from Age-Related Alterations

Dietary restriction maintains the basal rate of somatotrope renewal in later life in male rats

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