Since the synthesis and release of cortisol are regulated by pituitary corticotrophin, removal of the pituitary gland results in decreased function and eventual atrophy of the zona fasciculata and zona reticularis. Infusion of supraphysiological concentrations of cortisol will suppress corticotrophin secretion from the pituitary and will markedly decrease circulating corticotrophin levels. This occurrence implies a negative feedback control for corticotrophin and corticosteroid release (Fig. 60.3).
In addition to the humoral control of corticotrophin release, direct nervous control is mediated through the median eminence of the hypothalamus (Fig. 60.3). Nerve terminals in the median eminence store and release various hormones and neurotransmitters, including corticotropin-releasing factor (CRF), which is under the control of higher neural centers. During stress, CRF is released into the pituitary portal system to stimulate corticotrophin release. Activation of the hypothala-mic-pituitary system also accounts for the diurnal, or circadian, nature of cortisol secretion; plasma cortisol concentrations reach a maximum between 6 and 8 a.m. and then slowly decrease through the afternoon and evening. Human and animal studies suggest the existence of an early (fast) and more prolonged (delayed,
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