الفهرس 
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Abstract
Hashimoto thyroiditis is the most common endocrine disorder after diabetes mellitus.
It is characterized by the accumulation of antibodies against thyroid tissues. It affects
females more than males at a mild age. The pathogenesis of the disease is not completely
understood. Two types of antibodies are produced, TPO-Ab and Tg-Ab. Synthesis and
secretion of thyroid hormones (T3 & T4) decreased, while serum levels of TSH increased to
stimulate the secretion of thyroid hormones.
The circadian system is composed of many genes and proteins which control several
physiological and metabolic processes. It acts like an orchestra, regulated by two limbs, a
stimulatory and an inhibitory. The two limbs form a feedback loop. Clock systems are
regulated by the transcription and translation of circadian genes. Bmal-1 gene is an element
of the stimulatory limb, upregulates transcription of genes of the inhibitory limb and other
circadian controlled-genes. The proteins of the inhibitory limb, in turn, downregulates the
Bmal-1 gene. Melatonin is a circadian hormone secreted by the pineal gland mainly at
night. Melatonin rhythm is regulated by BMAL-1 protein and can affect thyroid cells.
The present study aimed at the evaluation of circadian clock gene Bmal-1 expression
in peripheral blood leukocytes and blood melatonin level of Egyptian patients with
Hashimoto’s thyroiditis.
The study was conducted on 60 Egyptian female volunteers and they were divided
into two groups: Hashimoto thyroiditis patients and normal control individuals. group I
(control group) consists of 30 normal Egyptian healthy females not receiving any type of
treatment. group II (Hashimoto thyroiditis patients) consists of 30 Egyptian females with
Hashimoto thyroiditis not receiving any type of treatment. Blood samples were collected
from all volunteers for the determination of different parameters including TSH, FT3, FT4,
TPO-Ab, Tg-Ab, ionized calcium, and Hemoglobin. Gene expression of Bmal-1, NF-κB,
and TLR-4 genes was determined using the RT-PCR method. Melatonin concentration in
serum was also determined using ELISA kits.
The current study results revealed increased serum TSH, TPO-Ab, and Tg-Ab in the
Hashimoto thyroiditis group in comparison to the control group. On the other hand, the
current study also showed decreased serum concentration of FT3, FT4, ionized calcium,
blood hemoglobin in the diseased group when compared to the control group.
The current study results revealed that the gene expression of the Bmal-1 gene in
peripheral blood leucocytes was downregulated in the Hashimoto thyroiditis group in
comparison to the control group. On the contrary, the levels of gene expression of NF-κB
and TLR-4 genes in peripheral blood leucocytes were upregulated in Hashimoto thyroiditis
in comparison to the control group. Finally, serum melatonin concentration decreased in
the diseased group when compared to the control one.