Selective autonomic nervous control of thyroid hormone and calcitonin secretion during metabolic and cardiorespiratory activation by intracisternal thyrotropin-releasing hormone (TRH)

Abstract

Injections of 10 μg/kg thyrotropin-releasing hormone (TRH) 150 μl intracisternally (i.c.) in conscious rabbits evoked behavioral excitation and compulsive scratching, tachypnoea, an increase of heart rate and blood pressure, oxygen consumption and hyperthermia. TRH i.c. significantly increased free thyroid hormone and calcitonin secretion during depressed thyrotropin (TSH) secretion. The rise of calcitonin correlated with a fall of serum calcium. The ergotropic function of TRH i.c. was further demonstrated by rapid increases of glucagon, serum glucose, free fatty acid and free glycerol, with a delayed rise of insulin depending on glucose levels. The increases of free thyroid hormones, calcitonin, cortisol and lipolysis following TRH i.c. were augmented after spinal transection, while glucagon secretion increased at a slower rate, however, not accompanied by rises of glucose and insulin. Behavioral excitation and lipolysis were augmented by TRH i.c. after total thyroidal denervation, which completely prevented the rise in thyroid hormone and calcitonin secretion, although the thyroid follicles and C cells responded properly to TSH. Section of all thyroidal nerves except the recurrent laryngeal nerve reduced mainly calcitonin secretion following TRH i.c., while the behavioral, autonomic and other endocrine responses were augmented. Additional abdominal vagotomy in these rabbits diminished glucagon secretion by about 50% without significantly changing the other effector responses. Taking 125I-labelled TRH concentration in the cerebrospinal fluid at the site of i.c. injection as 100%, then 58% of TRH penetrated into outer parts of the dorsal and ventral medulla oblongata and pons, and 8% into the neuropil of the aqueductal region. Radioactivity in other brain areas including the hypothalamus was below 1%, while the hypophysis was practically devoid of radiolabelled TRH. It is suggested that the observed behavioral, autonomic and endocrine activity pattern elicited by injection of TRH into the cisterna magna was caused by excitation of neurons confined to that compartment and was mediated by pathways of the reticular formation of the lower brainstem, with the concept that TRH-containing neurons are intrinsic excitatory constituents of the ‘activating reticular system’.