Regulatory role of gamma-aminobutyric acid in pituitary hormone secretion

Elias, Alan N.; Valenta, Lubomir J.; Szekeres, Agnes V.; Grossman, Marshall K.

doi:10.1016/0306-4530(82)90052-x

Cited by 42 publications

(24 citation statements)

References 94 publications

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“…Furthermore, our data argue in favor of the hypothesized negative GABAergic modula tion of ACTH secretion [3][4][5]. Such an inhibitory role of GABA on ACTH is not generally accepted, because some authors have been unable to demonstrate a clear effect of sodium valproate on the pituitary-adrenal axis, for example when it is stimulated by insulin-induced hypo glycemia [18].…”

Section: Discussionmentioning

confidence: 91%

“…of GABA, on ACTH secretion has been proposed [19]; therefore, as far as the present findings are concerned, SP also may be supposed to act at the hypothalamic level. Sodium val proate freely crosses the BBB [3,4], and thus it might have conditioned the ACTH response to SP by acting on nuclei located inside the BBB, such as the paraventricular nucleus where CRH is produced. This possibility is sup ported by the finding of a rich GABAergic innervation at this level [20,21], On the other hand, in vitro studies have suggested a possible site for GABAergic action on ACTH release at the pituitary level [22,23], Further studies are needed to establish the neuroana tomical site(s) where SP and GABA interact in the con trol of ACTH secretion.…”

Section: Discussionmentioning

confidence: 99%

“…These results prompted us to evaluate the possible influence of GABAergic neurotransmission on the ACTH/cortisol re sponse to SP. In fact, GABA has been shown to act as an inhibitory modulator of both ACTH secretion [3][4][5] and SP-mediated neurotransmission [6][7][8] in various experi mental conditions. Therefore, the ACTH/cortisol re sponse to the administration of SP was evaluated after treatment with sodium valproate, a drug which enhances the endogenous GABAergic tonus through inhibition of GABA transaminase [9],…”

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confidence: 99%

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Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Coiro

Capretti²,

Volpi

et al. 1992

Neuroendocrinology

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The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg^–1/min^–1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg^–1/min^–1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Coiro

Capretti²,

Volpi

et al. 1992

Neuroendocrinology

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“…The possibility that GABA is itself a pituitary tropin has been the subject of a wide range of in vivo and in vitro physiological studies, and is reviewed elsewhere (Elias et al, 1982;Ondo and Pass, 1976;Racagni et al, 1982;Tappaz, 1984). In brief, GABA may function as a prolactininhibiting factor via GABA receptors in the pituitary, although with less potency than dopamine (Enjalbert et al, 1979;Schally et al, 1977).…”

Section: Gaba Innervation Of Hypothalamic Dopaminergic Neuronsmentioning

confidence: 99%

“…In brief, GABA may function as a prolactininhibiting factor via GABA receptors in the pituitary, although with less potency than dopamine (Enjalbert et al, 1979;Schally et al, 1977). Injections of GABA, GABA agonists, and GABA antagonists into the cerebrospinal fluid have been reported to influence not only prolactin, but also gonadotropins, adrenocorticotropin, growth hormone, and thyrotropin (Elias et al, 1982;Racagni et al, 1982;Tappaz, 1984). The literature is too voluminous to review here, but it does underscore the importance of GABA in the brain as a modulator of hormones of the anterior pituitary and, through the pituitary, of endocrine organs including the gonads, thyroid, and adrenal.…”

Section: Gaba Innervation Of Hypothalamic Dopaminergic Neuronsmentioning

confidence: 99%

Tyrosine hydroxylase immunoreactive neurons throughout the hypothalamus receive glutamate decarboxylase immunoreactive synapses: a double pre- embedding immunocytochemical study with particulate silver and HRP

Pol¹

1986

J. Neurosci.

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Silver-intensified gold (SIG) particles were used for light-and electron-microscopic immunocytochemical localization of neuronal antigens, and the SIG method was compared with related heavy-metal methods for the purpose of dual ultrastructural localization of neurotransmitter-related antigens. SIG immunostaining was combined with peroxidase immunostaining to allow simultaneous study of differentially labeled tyrosine hydroxylase and glutamate decarboxylase immunoreactive neurons in the medial hypothalamus.A number of electron-dense markers that might be of use in double immunostaining for light and electron microscopy were examined, either with a simple nitrocellulose dot-blot method or on Formvar-coated slot grids. Of these, silver-intensified 5 nm colloidal gold was the most effective. Silver intensification of colloidal silver and of peroxidase reaction product also showed promise for combined LM and EM double-immunolabeling studies. Since the silver-intensification procedure used here intensifies both gold and peroxidase, in experiments involving double staining, the silver-intensified gold procedure should be used for the first antigen and nonintensified HRP for the second.Presumptive dopaminergic neurons containing the enzyme tyrosine hydroxylase were located throughout the hypothalamus with SIG immunostaining. In the same areas where frequent tyrosine hydroxylase immunoreactive neurons were found, many axons and bouton terminals were also found with antisera against GABA or against the GABA-synthesizing enzyme glutamate decarboxylase. Areas containing cells immunoreactive for tyrosine hydroxylase and stained with SIG and axons immunoreactive for glutamate decarboxylase and stained with peroxidase included the periventricular area (A14), the arcuate nucleus (A12), the dorsomedial hypothalamus/zona incerta area (A13), the posterior hypothalamus (All), the medial paraventricular nucleus, and dorsal to the supraoptic nucleus, in addition to the preoptic area near the third ventricle and dorsally adjacent to the anterior commissure. For comparison, the SIG procedure was also used to stain dopaminergic neurons outside the hypothalamus in the substantia nigra and ventral tegmental area. and electron microscopy. By virtue of a large silver shell formed around the colloidal gold particle and its adsorbed immunoglobulin or protein A, cross-reactivity of the first set of immunoreagents stained with particulate silver and a second set stained with peroxidase could be reduced or eliminated. To test its versatility, the SIG methodology was used to stain five other putative neurotransmitter-related antigens in the hypothalamus, including glutamate decarboxylase, somatostatin, prolactin, luteinizing hormone releasing hormone, and neurophysin in frozen sections or sections embedded in plastic, polyethylene glycol, or paraffin.In all areas examined ultrastructurally, including the arcuate nucleus (A12), the periventricular area (A14), the medial paraventricular nucleus, and the dorsomedial hypothalamus, glutamate decarboxy...

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Intravenous alprazolam challenge in normal subjects

et al. 1989

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Alprazolam, a novel benzodiazepine derivative is thought to be effective in the treatment of anxiety, panic, and depressive disorders. There is considerable interest in alprazolam's mechanism of action, particularly whether its profile of actions might resemble that of the alpha 2 adrenoreceptor agonist, clonidine. The present study assessed the biochemical, cardiovascular, and behavioral responses of healthy volunteers to acute intravenous infusions of alprazolam and placebo. Alprazolam reduced ACTH and cortisol while increasing growth hormone. There was a transient reduction in plasma norepinephrine and only modest effects on cardiovascular parameters. Subjects became quite sedated after intravenous alprazolam. This pharmacodynamic profile resembles that previously reported for traditional benzodiazepines, although alprazolam may be a more potent stimulator of growth hormone release. Alprazolam's effects on growth hormone resemble those of clonidine, but unlike clonidine, alprazolam has relatively little effect on plasma catecholamine and cardiovascular parameters. This suggests that alpha 2 mechanisms do not play a primary role in alprazolam's mode of action. Since alprazolam infusion affects three different measures (ACTH/cortisol, growth hormone, and plasma norepinephrine) thought to be dysregulated in depression, challenge with intravenous alprazolam may prove to be a useful "probe" in affective disorders.

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Regulatory role of gamma-aminobutyric acid in pituitary hormone secretion

Cited by 42 publications

References 94 publications

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Stimulation of ACTH/Cortisol by Intravenously Infused Substance P in Normal Men: Inhibition by Sodium Valproate

Tyrosine hydroxylase immunoreactive neurons throughout the hypothalamus receive glutamate decarboxylase immunoreactive synapses: a double pre- embedding immunocytochemical study with particulate silver and HRP

Intravenous alprazolam challenge in normal subjects

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