Al-Damluji, Saad; (1991) The adrenergic control of corticotrophin secretion. Doctoral thesis (M.D), UCL (University College London).

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Abstract

1. A highly selective alpha-1 adrenoceptor agonist that crosses the blood brain barrier stimulated the secretion of corticotrophin (ACTH) in man and in the rat in a dose - dependent manner. The effect was blocked by selective alpha-1 antagonists which also cross the blood brain barrier. It was concluded that activation of alpha-1 adrenoceptors stimulates ACTH secretion. A considerable amount of evidence obtained in the rat and in man suggested that the stimulant alpha-1 adrenoceptors are located in the brain, rather than directly on the pituitary gland or in the periphery. In the rat, the alpha-1 adrenoceptors stimulate ACTH secretion predominantly by activating hypothalamic vasopressin neurones. 2. Intravenous infusions of adrenaline and dopamine did not stimulate ACTH secretion or enhance the ACTH response to the corticotrophin releasing factor (CRF-41) in man. It was concluded that circulating catecholamines do not stimulate ACTH secretion under physiological conditions, and the peripheral sympathoadrenal response to stress is not responsible for the accompanying increase in ACTH secretion. 3. Activation of endogenous catecholamines increased ACTH secretion, suggesting that the stimulant alpha-1 adrenoceptors are innervated by catecholaminergic neurones and are likely to be physiologically relevant. 4. The physiological significance of the stimulant alpha-1 adrenoceptors in man was demonstrated in two situations: the cortisol secretory pattern during waking hours and the ACTH and cortisol responses to food ingestion were both enhanced by an alpha-1 agonist and reduced by an alpha-1 antagonist. Cortisol secretion at night and in response to hypoglycaemia were unaffected by an alpha-1 antagonist, suggesting that alpha-1 adrenoceptors mediate some but not all of the stimuli to ACTH secretion. 5. During some conditions of increased ACTH secretion, inhibitory alpha-2 adrenoceptors are activated and they limit the ACTH response. 6. The potential clinical applications of this work are discussed.

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