Actions of benzodiazepines on the neuroendocrine system

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 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 Kd of 11 nM and a Bmax of 27 fmol/10(6) cells. In cultures of anterior pituitary cells diazepam enhanced the inhibition of prolactin secretion produced by gamma-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.