Changes in Growth Hormone Secretion in Aging Rats and Man, and Possible Relation to Diminished Physiological Functions

Sonntag, William E.; Forman, Lloyd J.; Meites, Joseph

doi:10.1007/978-1-4684-4523-7_14

Cited by 13 publications

(5 citation statements)

References 167 publications

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“…There are potential problems in the evalu- MOR is known to increase GH by a central action on neurotransmitters, growth hormone releasing factor, and somatostatin (28). In the present study, MOR increased plasma GH to similar levels in control and E2-treated animals; however, a fourfold greater increase in GH was observed in animals 4 weeks after withdrawal of E2-treatment.…”

Section: Materials and Methods Animals And E2contrasting

confidence: 66%

Persistence of Low Hypothalamic Dopaminergic Activity after Removal of Chronic Estrogen Treatment

Gottschall¹,

Sarkar²,

Meites³

1986

Experimental Biology and Medicine

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\eitroendocrine Research Lahoraiori Departrnenl ( I / Ph~siologj Michigan Stare 1. nriersitj East Lansing Michigan 48824-1101 .4hsrracr. The purpose of this study was to determine whether inhibition of tuberoinfundibular dopaminergic (TIDA) neuron function uhich occurs during chronic estrogen administration persists after removal of the estrogen. Ovariectomized (OVX) Fischer 344 (F344) rats were implanted for 4 weeks with a Silastic capsule containing estradiol-17P (E2) and controls with an empty capsule for 4 weeks. Other rats which received E2 for 4 weeks had the capsule removed and experiments performed 4 weeks later. At the end of 4 weeks of E2 treatment, anterior pituitary (AP) weight was increased sixfold, serum prolactin (PRL) 65-fold, and AP DNA content fivefold over OVX control rats. Four weeks after removal of E2, AP weight, serum PRL, and AP DNA content declined, but remained significantly above OVX control values. At the end of 4 weeks of E2 treatment and after E2 withdrawal. release of ['Hldopamine (DA) from median eminence (ME) tissue superfused in riiro was lower than from ME of OVX control rats although ['HIDA accumulation was not significantly different among the treatment groups. Administration of apomorphine (APO), a dopamine agonist. significantly reduced plasma prolactin levels in OVX control rats, in rats at the end of 4 weeks E2 treatment. and in rats after 4 weeks of Ez withdrawal. Injection of haloperidol (HALO) produced similar increases in plasma PRL/estimated PRL-cell DNA in OVX controls. at the end of E2 treatment or after E2 withdrawal. However. injection of morphine (MOR), a drug uhich increases the release of PRL by inhibiting hypothalamic dopaminergic activity, resulted in a rise in plasma PRL/estimated PRL-cell DNA in OVX control rats that was significantly greater compared to rats at the end of E2 treatment or after E2 withdrawal.

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Section: Materials and Methods Animals And E2contrasting

confidence: 66%

Persistence of Low Hypothalamic Dopaminergic Activity after Removal of Chronic Estrogen Treatment

Gottschall¹,

Sarkar²,

Meites³

1986

Experimental Biology and Medicine

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“…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%

“…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). This suggests either an alteration in SRIF secretion by the hypothalamus or increased sensitivity to SRIF with age (41).…”

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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“…Progressively reduced GH secretion and in vivo GH responsiveness to physiological GH-releasing hormone (GRF) are evident in aging rodents (Sonntag et al, 1983;Cocchi et al, 1986) as well as in man (Rudman et al, 1981;Sonntag et al, 1983;Shibasaki et al, 1984). Also, the amount of immunoreactive GRF present in the median eminence of old rats is markedly reduced, while immunoreactive somatostatin is almost unchanged (Morimoto et al, 1988).…”

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confidence: 99%

Sexually Dimorphic Effects of Aging on Rat Somatotropes and Lactotropes

Rossi

Galbiati

et al. 1991

Journal of Gerontology

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During the aging process modified functions ofhypothalamic factors may cause sexually dimorphic changes in pituitary somatotropes and lactotropes. To test this hypothesis, pituitary tissue from young adult (4 months) and old (20-22 months) male and female rats was labeled immunocytochemically for growth hormone (GH) and prolactin (PRL). The total amount of immunoreactive material as well as the total area and number of immunoreactive structures were evaluated. With increasing age the intracellular GH content was moderately increased in male and decreased in female rats. An age-dependent PRL increase, due both to increased cell number and intracellular hormone content, was present only in female rats. The amount of GH-and PRL-immunoreactive material, distributed into classes of increasing density, differed both between sex and age groups. Our results indicate that the aging process of the somatotrope and lactotrope cell populations in rats appears to be different in the two sexes.

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Changes in Growth Hormone Secretion in Aging Rats and Man, and Possible Relation to Diminished Physiological Functions

Cited by 13 publications

References 167 publications

Persistence of Low Hypothalamic Dopaminergic Activity after Removal of Chronic Estrogen Treatment

Persistence of Low Hypothalamic Dopaminergic Activity after Removal of Chronic Estrogen Treatment

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

Sexually Dimorphic Effects of Aging on Rat Somatotropes and Lactotropes

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