The Diurnal Variation of Immunoreactive Thyrotropin-Releasing Hormone and Somatostatin in the Cerebrospinal Fluid of the Rhesus Monkey*

Abstract
TRH and somatostatin (SRIF) are present in high concentrations in the hypothalamus (where they function as regulators of pituitary TSH and GH secretion) and also in the extrahypothalamic brain (where they may act as peptidergic neuromodulators). Both peptides are present in the cerebrospinal fluid (CSF), though their source is not known. Since there are diurnal variations in the CSF concentrations of other neurotransmitters, in pituitary hormone secretion, and in the behavioral responses to TRH and SRIF administration, it was of interest to study the diurnal variation of CSF TRH and SRIF in CSF. CSF was continuously withdrawn from chair-restrained rhesus monkeys, and 2-h fractions were assayed for SRIF and TRH. CSF did not exhibit nonspecific RIA effects, and peptide recoveries through the collection procedure were 70–100%. TRHlike and SRIF-like immunoreactivities in CSF eluted as single peaks on reverse phase high pressure liquid chromatography with retention times similar to those of synthetic TRH and SRIF. TRH-like immunoreactivity (mean, 34 ± 2 pg/ml; n = 159) in CSF showed a significant overall diurnal variation (P < 0.005), with maximal concentrations occurring in the afternoon (1613 h). SRIF-like immunoreactivity (mean, 82 ± 3 pg/ml; n = 362) in CSF also showed a significant overall diurnal variation (P < 0.005), with maximal concentrations occurring at night (0049 h). In individual monkeys, the pattern was less readily demonstrated, with nocturnal elevations present in four monkeys, a reversed pattern in one, and a biphasic pattern ifi another. Fluctuations of TRH and SRIF in CSF may reflect hypothalamic secretion, since they parallel variations reported in serum TSH and GH, or they may reflect changes in TRH and SRIF in the extrahypothalamic brain. Further study of these rhythms may be useful in differentiating the roles of TRH and SRIF in various brain localizations.

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