Serotoninergic Control of Growth Hormone Secretion: Hypothalamic Dopamine, Norepinephrine, and Serotonin Levels and Metabolism in Three Hyposomatotropic Rat Models and in Normal Rats*

Abstract

The relationship between the activity of the brain biogenic monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) and pituitary GH release remains controversial due to the previous use of indirect and nonspecific techniques. The aim of this investigation was to determine directly and specifically the relative activities (turnover) of hypothalamic DA, NE, and 5-HT in rat models of pituitary GH deficiency and GH hypo-or hypersecretion. These models were 1) adult rats after neonatal monosodium-L-glutamate (MSG) treatment, 2) hypophysectomized rats with and without GH replacement, 3) hypothyroid [propylthiouracil (PTU)-treated] rats, and 4) normal rats. Selected ion monitoring (computerized gas chromatography-mass spectrometry) was used to specifically and simultaneously assay hypothalamic concentrations of DA, NE, and 5-HT and their major metabolites. The turnover or activity of each amine in the hypothalami was estimated from the ratio of metabolite to amine in each case as well as by the use of the monoamine oxidase inhibitor pargyline for MSG-treated rats.In MSG-treated rats, there was a marked reduction (P < 0.0025) in the hypothalamic turnover of 5-HT which was associated with a significant fall (P < 0.05) in serum GH concentrations. In hypox rats, there was found to be a highly significant increase (P < 0.01) in hypothalamic 5-HT turnover, which was corrected to control levels after a course of GH treatment. In the hypothyroid rats, there was also a highly significant increase in the hypothalamic ratio of 5-hydroxyindoleacetic acid to 5-HT within 6 days of commencing PTU treatment, and this ratio remained elevated (P < 0.0025) after 38 days PTU uptake. This increased 5-HT activity was associated with a significant increase in GH secretion (P < 0.01; by 6 days), but after 38 days on PTU, when pituitary GH was depleted, serum levels were significantly less (P < 0.05) than controls. In the group of normal rats, 10 of 44 of the animals exhibited very high GH concentrations (>250 ng/ml). The mean hypothalamic 5-hydroxyindoleacetic acid to 5-HT ratio in these animals was highly significantly greater (P < 0.0005) than that in the remaining 34 animals, all of which had serum GH levels below 90 ng/ml. We propose that the high 5-HT turnover and high serum GH concentrations are directly related. There was no relationship between turnover or concentrations of DA or NE and GH status in these studies.The conclusions from this investigation are that hypothalamic 5-HT activity is directly related to GH secretory status in the rat and that serotoninergic pathways participate in GH negative feedback effects in the hypothalamus. (Endocrinology 110: 376, 1982) T HE ROLES of specific monoamine neuronal pathways in the central stimulation of GH release have yet to be convincingly elucidated. The case of central control of GH is a particularly confusing one, and in a recent review, Krulich (1) cited considerable evidence favoring a role for all three major brain monoamines, dopamine (DA), norepinephrine (NE), and s...

Effects of 6-Methoxy-l,2,3,4-tetrahydro-b-carboline and Yohimbine on Hypothalamic Monoamine Status and Pituitary Hormone Release in the Rat

“…Ltd., North Ryde, N.S. W., Australia) with deuterated internal standards, extraction and derivatization procedures being identical to those previously described (Smythe et al 1982a). The between-assay coefficient of variation for the various compounds assayed ranged from 2·5 to 7·0 %.…”

“…The mean wet weight of the MBH samples for all the studies reported here was 18 ·0±1· 8 (s.d.) mg. MBH samples were mechanically homogenized (Ultra-Turrax) in 1 ml of a solution of 5 M formic acid in n-butanol (1:4 v/v) which contained calibrated amounts of deuterated standards for the monoamines and metabolites (see Smythe et al 1982a). …”

“…These changes were proposed (Buckholtz 1980b) to be primarily due to inhibition by 6-MeOTHBC of neuronal 5-HT uptake. Regardless of its precise mode of action, the ability of 6-MeOTHBC to markedly reduce the ratio of 5-HIAAj5-HT in mouse brain strongly indicates that this compound reduces central 5-HT neuronal activity (see Smythe et al 1982aSmythe et al , 1982b. As a consequence 6-MeOTHBC should inhibit the secretion of pituitary growth hormone (GH) and thyroid stimulating hormone (TSH) which are both under stimulatory control by hypothalamic 5-HT neuronal activity (Smythe et al 1982a(Smythe et al , 1982b.…”

“…Regardless of its precise mode of action, the ability of 6-MeOTHBC to markedly reduce the ratio of 5-HIAAj5-HT in mouse brain strongly indicates that this compound reduces central 5-HT neuronal activity (see Smythe et al 1982aSmythe et al , 1982b. As a consequence 6-MeOTHBC should inhibit the secretion of pituitary growth hormone (GH) and thyroid stimulating hormone (TSH) which are both under stimulatory control by hypothalamic 5-HT neuronal activity (Smythe et al 1982a(Smythe et al , 1982b. Furthermore, the stimulatory effect of 6-MeOTHBC on corticosterone release in mice indicates that this compound also increases central noradrenaline (NA) neuronal activity which we have shown to be a specific stimulus to pituitary adrenocorticotrophin (ACTH) release (Smythe et al 1983).…”

“…Computerized gas chromatography-mass spectrometry using deuterated internal standards provides a method of analysing brain monoamine and metabolite concentrations with high precision and specificity (Smythe et al 1982a(Smythe et al , 1983. In the present investigation this technique was used to obtain the concentrations of hypothalamic monoamines and their metabolites for the assessment of monoamine neuronal activity by the metabolic ratio method.…”