The involvement of serotonin in regulation of pituitary-adrenocortical function.

Adrenocorticotropin (ACTH) secretion from the anterior pituitary gland influences glucocorticoid secretion from the adrenal cortex and in turn is controlled mainly by corticotropin-releasing factor (CRF) release from the hypothalamus. CRF-containing neurons projecting from the paraventricular nucleus to the median eminence, which are involved in controlling pituitary-adrenocortical function, receive synaptic input from serotonin neurons projecting from the midbrain raphe nuclei. Serotonin stimulates the release of bio- or immunoassayable CRF from isolated rat hypothalamus in vitro. Corticosterone, ACTH, and CRF release in vivo is increased in rats by drugs that enhance serotonin function, including serotonin precursors, serotonin uptake inhibitors, serotonin releasers, and direct-acting serotonin agonists. Among the multiple serotonin receptors that exist in brain, at least two--5HT1A and 5HT2 or 5HT1C receptors--seem to mediate activation of pituitary-adrenocortical function. The physiological role of this stimulatory serotonergic influence on pituitary-adrenocortical function is still not well understood, but serotonin may play a role in circadian rhythmicity of adrenocortical secretion and in the activation of pituitary-adrenocortical function by certain types of stress. Measurement of ACTH or cortisol levels in humans after administration of a direct- or indirect-acting serotonin agonist provides one means of probing the functional state of brain serotonergic systems in disease or after drug treatment.