Twenty-four-Hour Rhythms of Serum Acth, Prolactin, Growth Hormone, and Thyroid-Stimulating Hormone, and of Median-Eminence Norepinephrine, Dopamine, and Serotonin, in Rats Injected with Freund's Adjuvant

Abstract

The effect of Freund's adjuvant injection on 24-h variation of circulating ACTH, prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH) levels, and of norepinephrine (NE) content, and dopamine (DA) and serotonin (5HT) turnover in median eminence, was examined in adult rats kept under light between 0800 and 2000 h daily. Groups of 6-10 animals received Freund's complete adjuvant or its vehicle at 1100 h 3 days before sacrifice and were killed by decapitation at six different time intervals throughout a 24-h cycle. In rats injected with adjuvant's vehicle, serum ACTH and prolactin exhibited peak values around the light-dark transition (p < 0.0001 and < 0.04, respectively), while the maximum in TSH was found in the late afternoon (p < 0.0001, one-way ANOVA). GH levels did not vary on a 24-h basis. In Freund's adjuvant-injected rats, 24-h variations of TSH levels became blunted, while 24-h variations of prolactin and ACTH persisted. Freund's adjuvant augmented serum ACTH and prolactin levels, and decreased GH and TSH levels (p < 0.0007, factorial ANOVA). Median-eminence NE content, and turnover of DA, assessed by measuring dihydroxyphenylacetic acid, DOPAC/DA ratio, and of 5HT, assessed by measuring 5-hydroxyindoleacetic acid, HIAA/5HT ratio, varied on a 24-h basis in rats receiving adjuvant's vehicle (p < 0.02). Median-eminence NE content attained its maximum at 1600-2000 h, while maxima in DOPA/DA and HIAA/5HT ratios occurred at 0400 h. Injection with Freund's adjuvant reduced the amplitude of the daily variation of NE content, shifted the maximum of DOPAC/DA ratio toward the light-dark transition, and blunted the daily variation in HIAA/5HT ratio in median eminence. The administration at 1200 of the immunosuppressant drug cyclosporine (5 mg/kg, 5 days) restored the augmented ACTH and prolactin levels (p < 0.0001, factorial ANOVA) and depressed GH and TSH levels (p < 0.02) found in Freund's adjuvant-injected rats. Cyclosporine was also effective in restoring 24-h rhythmicity of serum ACTH and TSH, but not of prolactin, levels. Cyclosporine did not modify the effect of Freund's adjuvant on time-of-day changes of median-eminence NE content, but it was effective in counteracting the changes of DA and 5HT turnover found after immunization. The results are compatible with a significant effect of immune-mediated inflammatory response at an early phase after Freund's adjuvant injection on ACTH, GH, prolactin, and TSH release, which is partially sensitive to immunosuppression by cyclosporine.

Age-Dependent Changes in 24-Hour Rhythms of Thymic and Circulating Growth Hormone and Adrenocorticotropin in Rats Injected with Freund’s Adjuvant

“…We previously reported changes in the 24-hour rhythms of adenohypophysial hormone release and hypothalamic monoamine and neuropeptide content during Freund's adjuvant arthritis in rats. Our results were compatible with significant effects of immunemediated inflammatory response on hormone secretory processes, which were partially sensitive to immunosuppression by cyclosporine [24][25][26]. These as well as other studies indicated that significant changes in 24-hour rhythms did occur during experimental arthritis in rats [27][28][29][30][31][32][33][34][35].…”

“…Changes in cir-Esquifino/García Bonacho/Arce/Cutrera/ Cardinali cadian rhythms are apparent at an early phase of experimental arthritis in rats and persist thereafter [29][30][31][32]46]. In previous studies we reported significant effects of immune-mediated inflammation on 24-hour variations of ACTH, GH, LH, testosterone, prolactin and TSH release after Freund's adjuvant injection to young adult [24,25] and old rats [33]. In old rats, 24-hour rhythms of circulating TSH, LH and testosterone became blunted.…”

Effect of Melatonin on 24-Hour Rhythms of Ornithine Decarboxylase Activity and Norepinephrine and Acetylcholine Synthesis in Submaxillary Lymph Nodes and Spleen of Young and Aged Rats

“…In every case, mesor and amplitude of 24-hour rhythm in ornithine decarboxylase activity were lowest in old rats. In a previous study carried out 3 days after Freund’s adjuvant injection in rats, increased levels and a modified 24-hour rhythmicity of circulating ACTH, and abolition of 24-hour rhythmicity of circulating thyroid-stimulating hormone were reported [46]. Presumably, the chronic stress condition given by mycobacterial adjuvant injection is instrumental in inhibiting a number of circadian rhythms at an early, as well as a late, phase of the disease.…”

IGF-I and IGF-I-binding proteins in rats with adjuvant-induced arthritis given recombinant human growth hormone

“…A decrease in serum growth hormone (GH) and pituitary GH mRNA has been described during the early phase before and after the disease develops (Neidhart & Flückiger 1992, Selgas et al 1997. We have recently reported that the decrease in GH mRNA is concomitant with a decrease in serum and hepatic insulinlike growth factor-I (IGF-I) that correlates with the decrease in body weight in arthritic rats (López-Calderón et al 1999).…”