Abstract
Evidence has been provided for impaired neurotransmitter functioning in the brain of elderly subjects. In order to assess central GABAergic transmission, the activity of the hypothalamic GABA system may be investigated by basal growth hormone (GH) response to the GABAergic drug sodium valproate (SV). For this purpose 15 healthy men (aged 19–81 years) received orally 800 mg SV or placebo tablets on two different occasions, 1 week apart. Blood samples were collected before and after drug administration for determining GH and SV plasma levels. A clearcut increase in plasma GH was observed following SV (P<0.001 in young persons,P<0.005 in old subjects), but in the aged subjects this rise was statistically lower than in the young men (P<0.001 at t=90 min). No difference was observed in basal GH levels and in SV plasma concentrations between elderly and young subjects. ΔGH (= maximum post-SV GH level minus baseline GH value) was significantly inversely related to age (r=-0.90,P<0.001). These results may suggest an impaired hypothalamic-pituitary responsiveness to a pharmacological challenge enhancing endogenous GABA tone in the elderly.
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References
Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79
Bruni JF, Mioduszewski RJ, Grandison LJ, Simpkins JW, Meites J (1977) Effects of cholinergic and GABAergic drugs on serum growth hormone (GH) in male rats. Fed Proc 36:323
Cavagnini F, Invitti C, Di Landro A, Tenconi L, Maraschini C, Girotti G (1977) Effects of gamma-aminobutyric acid (GABA) derivative baclofen, on growth hormone and prolactin secretion in man. J Clin Endocrinol Metab 45:579–584
Cavagnini F, Benetti G, Invitti C, Ramella G, Pinto M, Lazza M, Dubini A, Marelli A, Müller EE (1980) Effect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidone. J Clin Endocrinol Metab 51:789–792
Demarest KT, Moore KE, Riegle GD (1982) Dopaminergic neural function, anterior pituitary dopamine content, and serum concentrations of prolactin, luteinizing hormone and progesterone in the aged female rat. Brain Res 247:347–354
Elias AN, Valenta LJ, Szekeres AV, Grossman LK (1982) Regulatory role of gamma-aminobutyric acid in pituitary hormone secretion. Psychoneuroendocrinology 7:15–30
Enna SJ, Strong R (1981) Age-related alterations in central nervous system neurotransmitter receptor binding. In: Enna SJ, Samorajski T, Beer B (eds) Brain neurotransmitters and receptors in aging and age-related disorders. Raven, New York, pp 133–142
Enna SJ, Samorajski T, Beer B (1981) Brain neurotransmitters and receptors in aging and age-related disorders. Raven, New York
Fiok J, Acs Z, Makara GB, Erdo SL (1984) Site of gamma-aminobutyric acid (GABA)-mediated inhibition of growth hormone secretion in the rat. Neuroendocrinology 39:510–516
Fioretti P, Melis GB, Paoletti AM, Parodi G, Caminiti F, Corsini GU, Martini L (1978) Gamma-amino-beta-hydroxybutyric acid stimulates prolactin and growth hormone release in normal women. J Clin Endocrinol Metab 47:1336–1340
Godin Y, Heiner L, Mark J, Mandel P (1969) Effects of di-n-propylacetate, an anticonvulsant compound, on GABA metabolism. J Neurochem 16:869–873
Gregerman RI, Bierman EL (1974) Aging and hormones. In: Williams RH (ed) Textbook of endocrinology. WB Saunders, Philadelphia, pp 1059–1070
Kendall DA, Strong R, Enna SJ (1982) Modifications in rat brain GABA receptor binding as a function of age. In: Giacobine E, Filogano G, Vernadakis A (eds) The aging brain: cellular and molecular mechanisms of aging in the nervous system. Raven, New York, pp 211–221
Koulu M, Lammintausta R, Dahlströhm S (1980) Effects of some gamma-aminobutyric acid (GABA)ergic drugs on the dopaminergic control of human growth hormone secretion. J Clin Endocrinol Metab 51:124–129
Liljequist S, Engel JA (1984) Reversal anticonflict action of valproate by various GABA and benzodiazepine antagonists. Life Sci 34:2525–2533
Löscher W, Siemes H (1984) Valproic acid increases gamma-aminobutyric acid in CSF of epileptic children. Lancet II:225
Meites J (1981) Changes in hypothalamic regulation of pituitary function in aging rats. In: Enna SJ, Samorajski T, Beer B (eds) Brain neurotransmitters and receptors in aging and age-related disorders. Raven, New York, pp 107–115
Monteleone P, Maj M, Iovino M, Steardo L (1986) Growth hormone response to sodium valproate in chronic schizophrenia. Biol Psychiatry 21:588–594
Negro-Vilar A, Vijayan E, McCann SM (1980) The effect of intraventricular gamma-aminobutyric acid (GABA) on hypothalamic catecholamines and LH-RH and pituitary hormone release. Brain Res Bull 5:239–244
Racagni G, Apud JA, Cocchi D, Locatelli V, Müller EE (1982) GABAergic control of anterior pituitary hormone secretion. Life Sci 31:823–838
Simpkins JW, Mueller GP, Huang HH, Meites J (1977) Evidence for depressed catecholamines and enhanced serotonin metabolism in aging male rats: possible relation to gonadotropin secretion. Endocrinology 100:1672–1678
Spiess J, Rivier J, Vale W (1983) Characterization of rat, hypothalamic growth hormone releasing factor. Nature 303:532–535
Steardo L, Iovino M, Monteleone P, Agrusta M, Orio F (1985) Evidence for a GABAergic control of the exercise-induced rise in GH in man. Eur J Clin Pharmacol 28:607–609
Steardo L, Iovino M, Monteleone P, Agrusta M, Orio F (1986) Pharmacological evidence for a dual GABAergic regulation of growth hormone release in humans. Life Sci (in press)
Takahara J, Yunoki S, Yakushiji W, Yamaguchi J, Yamane Y, Ofuji T (1977) Stimulatory effects of gamma-hydroxybutyric acid on growth hormone and prolactin release in humans. J Clin Endocrinol Metab 44:1014–1017
Takahara J, Yunoki S, Hosogi H, Yakushiji W, Kageyama J, Ofuji T (1980) Concomitant increases in serum growth hormone and hypothalamic somatostatin in rats after injection of gamma-aminobutyric acid, aminooxyacetic acid or gamma-hydroxybutyric acid. Endocrinology 106:343–347
Tamminga CA, Neophytides A, Chase TN, Frohman A (1978) Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist. J Clin Endocrinol Metab 47:1348–1351
Van der Laan JW, De Boer T, Bruinvels J (1979) Di-n-propylacetate and GABA degradation. Preferential inhibition of succinic semialdehyde dehydrogenase and indirect inhibition of GABA-transaminase. J Neurochem: 32:1769–1780
Vijayan E, McCann SM (1978) Effects of intraventricular injection of gamma-aminobutyric acid (GABA) on plasma growth hormone and thyrotropin in conscious ovariectomized rats. Endocrinology 103:1888–1893
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Monteleone, P., Iovino, M., Orio, F. et al. Impaired growth hormone response to sodium valproate in normal aging. Psychopharmacologia 91, 10–13 (1987). https://doi.org/10.1007/BF00690918
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DOI: https://doi.org/10.1007/BF00690918