Endocrine Abstracts

The hypo and hyperthyroidism alter the synthesis/secretion of pituitary hormones, which in normal conditions present fluctuations in serum concentration during the 24h period. An intrinsic pituitary circadian clock might be related to these oscillations; however, the possible interaction between thyroid hormonal conditions and circadian clock gene expression in anterior pituitary is still unknown. The purpose of this study was to investigate the expression of core circadian clock as Bmal1, Per2 and Clock, and Tshb, Prl, Lhb and Dio2 as markers of thyrotroph, lactotroph, gonadotroph function and thyroid hormone action respectively, during hypo and hyperthyroidism in rats.

For this, male Wistar rats were divided in euthyroid, hypothyroid (thyroidectomized rats) and hyperthyroid (euthyroid animals treated for 5 days with T3: 1.5 μg/100g BW, twice a day) and euthanized every 3h, during 24h. The pituitaries were excised and the mRNA expression was evaluated by RT-qPCR, using Rpl19 as internal control. One and Two-way ANOVA, as well as, cosinor analysis were used to evaluate the time-of-day-dependent differential expression for each gene/group and their interactions.

The expression of Bmal1, Per2, Dio2, Prl and Lhb presented a circadian rhythmicity in anterior pituitary of euthyroid rats. Per2 and Dio2 acrophases occurred around ZT 12, while Bmal1, Lhb and Prl were at ZT 0/24. In the hypo and hyperthyroid animals, the circadian pattern of Per2, Prl and Lhb was abolished. Bmal1 expression lost its circadian pattern during hypothyroidism, while the hyperthyroidism reduced its acrophase and mesor values. In hypothyroid animals the acrophase of Dio2 was advanced and mesor was higher than in euthyroid rats, while in hyperthyroidism its circadian pattern was lost.

Our study reveals that the expression of core clock components in anterior pituitary gland are altered during the hyper and hypothyroidism, which might contribute to the altered secretion of pituitary hormones observed in these pathological conditions.