Disturbance in neuroendocrine regulation

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Disturbance in neuroendocrine regulation

The neuroendocrine system (NES) of Vertebrates can be defined as a set of cells organized in single organs and diffuse elements, sharing co-production of amine hormone/transmitters, peptide hormone/transmitters and specific markers of neural determination. In this perspective, the hypothalamic-pituitary-target organ axis (H-P axis), the autonomic nervous system (ANS) and the diffuse neuroendocrine or APUD system contribute to the NES.

The consequences of ageing of the neuroendocrine system have been incriminated in the development of various age-dependent conditions, such as insulin resistance, osteoporosis, muscular atrophy and abnormalities of fat deposition. Ageing affects the endocrine system by altering endocrine cells, the hormones produced by these cells and hormone receptors or postreceptor processes in the target cells.

Dopaminergic innervation of the hypothalamus comprises at least three neuronal systems. These are the tuberinfundibular dopamine system, the tuberohypophyseal dopamine system, and the incertohypothalamic dopamine system. The tuberinfundibular dopamine system shows the most dramatic age-related changes. Marked decreases in dopamine concentrations with age have been observed in the medial basal hypothalamus, containing primarily tuberinfundibular dopamine neurons. In contrast to the tuberinfundibular system, the tuberohypophyseal and ncertohypothalamic dopamine systems show varying responses to aging. Dopamine receptors can be divided into two major subtypes: D-1 and D-2. Age-related decreases in D-2 receptor subtypes occur in the caudate nucleus, putamen, substantia nigra and globus pallidus. In contrast, D-1 receptors have been reported to increase or show no change with age. There is a steady decline in dopaminergic cells in the substantia nigra with age in humans. The number of dopaminergic neurones in each substantia nigra declines from 400 000 at birth to 250 000 at age 60.

The serotonin (5-HT) responses to increasing age are variable. Total brain 5-HT levels decrease with age, but hindbrain 5-HT levels do not change. Depression is associated with a depletion of noradrenaline and serotonin. Age-related increase in MAO (monoamine oxidase) in the brain, which breaks down 5-HT and noradrenaline to 5-hydroxyindoleacetic acid and 4-hydroxy 3-methoxy D-mandelic acid, may predispose elderly people to depression. Serotonin is one of the main regulators of circadian sleep/wake cycles, and deficiency of serotonin is associated with many psychiatric and neurological disorders, including sleep disorders and some forms of dementia.

Episodic GH secretion becomes markedly impaired with ageing. This is due to a reduction in pulse amplitude, although pulse frequency remains unchanged. Sleep-related secretion of GH appears to be primarily dependent on the release of GH-releasing hormone. Age-related decrements in sleep-related GH secretion may play a role in the hyposomatotropism of senescence. Catecholaminergic alterations in the hypothalamus may be responsible for the reduced GH secretion in old age, as suggested by the restoration of GH pulse amplitudes in old male rats by repetitive injections of catecholamine precursors. Since acetylcholine inhibits hypothalamic somatostatin release, the reduced cholinergic tone in elderly subjects may result in an increased somatostatinergic tone.