Inhibition of cold-induced TSH release by benzodiazepines

doi:10.1016/0006-8993(83)90353-0

Brain Research

Volume 265, Issue 2, 18 April 1983, Pages 339-343

https://doi.org/10.1016/0006-8993(83)90353-0 Get rights and content

Abstract

Diazepam (1–5 mg/kg, i.p.) did not alter basal thyroid-stimulating hormone (TSH) release in rats; however, both diazepam (2 mg/kg, i.p.) and clonazepam (1 mg/kg, i.p.) blocked the 3–5-fold increase in TSH induced by cold exposure. The benzodiazepine antagonist, Ro15-1788 (10 mg/kg, i.p.) was effective in reversing clonazepam inhibition of cold-induced TSH release, but when administered alone had no effect on either basal TSH levels or the rise in TSH following cold exposure. Diazepam did not affect the ability of TRH to increase TSH secretion.

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Neuroendocrine effects of benzodiazepines
1990, Journal of Psychiatric Research
Benzodiazepine administration has been associated with alterations in neuroendocrine function both in experimental animals and in humans. Clinical and laboratory data indicate that the beta-carbolines, a class of active benzodiazepine receptor inverse agonists, cause behavioral and neuroendocrine changes characteristic of anxiety and stress. In contrast, the “classic” benzodiazepine receptor agonists such as diazepam can reduce anxiety and inhibit stress-induced increases in anterior pituitary hormone secretion.
Although the site of action and mechanisms by which benzodiazepines alter anterior pituitary hormone secretion are still under investigation, evidence suggests that the effects are mediated in the brain, primarily through actions at benzodiazepine receptors in the hypothalamus. The benzodiazepines may act at GABA-coupled benzodiazepine receptors in the hypothalamus or other regions of the brain to potentiate the effects of endogenous GABA. It also is believed that brain monoamines may modulate the effects of endogenous GABA. Brain monoamines have also been reported to modulate the effects of benzodiazepines on stress-induced hypothalamic-pituitary-adrecortical function. Direct effects of the benzodiazepines on central- and peripheral-type benzodiazepine receptors in the anterior pituitary have also been documented.
Diazapam: Endocrine effects and hypothalamic binding sites in the developing male and female rat
1989, Life Sciences
The ontogeny of diazepam's endocrine effects in male and female rats, and of ³H-diazepam binding in the hypothalami of both sexes was studied. Diazepam inhibited basal prolactin levels in 38 day-old male rats and, if prolactin levels were stimulated by Haloperidol the inhibition occurred in 28 day-old males, indicating that the hypoprolactinemic effect of the drug could be evidenced earlier if prolactin titers were high. The prolactin inhibition in females did not reach statistical significance at any studied age. Diazepam significantly released LH only in male rats at 12 days, showing thus, a period of special sensitivity of LH release to the drug.
Benzodiazepine-hypothalamic binding sites increased in number from birth to puberty, reaching a plateau at 20 days of age. No sexual differences or changes in affinity were found throughout the studied period.
These results suggest that the maturtion of diazepam's hypoprolactinemic effect could be partially related to the increase in hypothalamic binding sites, whereas the sexual differences observed in diazepam's endocrine actions could be due to sexual differentiation of endocrine control mechanisms.
Actions of benzodiazepines on the neuroendocrine system
1983, Neuropharmacology
The administration of benzodiazepines to rats is associated with alterations in the secretion of anterior pituitary hormones. Although basal secretion of prolactin and thyroid stimulating hormone (TSH) was not changed by benzodiazepines, the secretory response to physiological and pharmacological stimuli was attenuated. Diazepam reduced the rise in secretion of prolactin during proestrus and the increase in release induced by stress, administration of fluoxetine plus 5-hydroxytryptophan and haloperidol. Diazepam also blocked the rise in release of TSH induced by exposure to cold. To establish the site at which benzodiazepines act, anterior pituitary binding for [³H]diazepam was characterized. Scatchard analysis indicated a K_d of 11 nM and a B_max of 27 fmol/10⁶ cells. In cultures of anterior pituitary cells diazepam enhanced the inhibition of prolactin secretion produced by γ-aminobutyric acid (GABA) and dopamine. The potency of benzodiazepine analogues established that the benzodiazepine binding site in the pituitary belonged to the peripheral subtype of benzodiazepine receptors. However, the potency of analogues for inhibition of the release of prolactin and TSH following systemic administration indicates that benzodiazepines with affinity for the central subtype of receptors were the most potent. These data are interpreted to suggest that the actions of benzodiazepines on the neuroendocrine system result from their actions within the CNS on the neurons involved in the regulation of pituitary function. In addition, peripheral benzodiazepine receptors are present on cells of the anterior pituitary and these binding sites can modulate secretion of prolactin in response to its inhibitory regulators.
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Benzodiazepine Dependence: Causalities and Treatment Options
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: A preliminary account of this work was presented at FASEB, New Orleans LA, 1982.

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Inhibition of cold-induced TSH release by benzodiazepines

Abstract

Europ. J. Pharmacol.

Specific benzodiazepine receptors in rat brain characterized by high affinity [3H]diazepam binding

Molecular mechanisms in the receptor action of benzodiazepines

Ann. Rev. Pharmacol. Toxicol.

Fear-dependent variations in continuous avoidance behavior in pigs

Psychopharmacology

[3H]Diazepam binding in mammalian central nervous system: a pharmacological characterization

J. Neurosci.

GABA-benzodiazepine interactions: physiological, pharmacological and developmental aspects

Characterization of benzodiazepine binding and action on rat anterior pituitary cells

Soc. Neurosci. Abstr.

Suppression of prolactin secretion by benzodiazepines in vivo

Neuroendocrinology

Changes in serum TSH level after intraventricular injection of various neuromediators in rats

Acta Endocr.

Specific benzodiazepine receptors in rat brain characterized by high affinity [³H]diazepam binding

[³H]Diazepam binding in mammalian central nervous system: a pharmacological characterization