All of the functions of the thyrocytes described in the previous section are under the control of thyroid-stimulating hormone (TSH) from the pituitary, which in turn is secreted in response to thyrotrophin releasing hormone (TRH) from the median eminence of the hypo thalamus. The structures of the tripeptide TRH and the heterodimeric TSH were described in Chapter 3. Figure 1 outlines this hypothalamic-pituitary-thyroid axis. The physiological stability of the rates of secretion of TSH and the thyroid hormones are primarily due to (1) the stimulation of TSH by TRH from the hypothalamus; (2) the effects of TSH on thyroid hormone pro duction and secretion; and (3) the feedback effects of T4 and T3 on the pituitary and hypothalamus.

Fig1. The hypothalamic-pituitary-thyroid axis. Control of thyroid hormone involves stimulation of pituitary TSH (thyroid stimulating hormone) by TRH (thyrotropic releasing hormone) from the hypothalamus. Many signals from other areas of the brain, such as cold and stress, influence TRH secretion by the hypothalamus. TSH stimulates synthesis and release of T4 (and some T3) from the thyroid gland. T4 is deiodinated to T3 (green ovals: T4→T3) in peripheral target tissues as well as in the pituitary and in the hypothalamus. The circulating thyroid hormones (purple oval) exert feedback inhibition on TSH secretion in the pituitary and, to a variable degree depending on species, on TRH secretion. Somatostatin (SRIF; SST) and dopamine (DA) also influence TSH secretion. Stimulatory and inhibitory effects are represented by solid and dashed lines, respectively.

The TRH which participates in this control system is synthesized in hypophysiotropic neurons of the par ventricular nucleus of the hypothalamus, whose axons project to the anterior pituitary where TSH is released. Destruction of these neurons leads to hypothyroidism, demonstrating their vital role in the tonic secretion of TSH by the pituitary. Additional neuroendocrine interactions take place between the hypothalamus and the pituitary, including the β-adrenergic-mediated increase in TRH secretion in response to cold or stress. Somatostain (SST) and dopamine, two hypothalamic hormones known for their roles in the control of growth hormone and prolactin secretion, respectively (see Chapter 3), exert an inhibitory influence on TSH secretion.

In the thyrotrophs of the pituitary gland, TRH inter acts with its specific G-protein coupled receptor which, through the phospholipase C catalyzed hydrolysis of phosphatidyl inositol to IP3 and diacylglycerol (DAG) leads ultimately to the stimulation of the transcription of TSHβ. The production of this subunit of the TSH heterodimer is the rate-limiting step in its assembly for TSH secretion. Protein kinase A-dependent pathways may also play a role in TRH-regulation of TSHβ gene transcription. In addition to its effects on TSHβ gene transcription, TRH also affects the bioactivity of TSH by altering its glycosylation pattern.

Circulating levels of T3 and T4 exert classic negative feedback effects on the pituitary secretion of TSH. The thyrotrophs of the pituitary gland contain high levels of deiodinase type II (D2) so that T4 is readily con verted to T3 which then interacts with the thyroid hormone receptor,TR, to inhibit transcription of both the α and β subunits. This effect on the β-subunit is much more rapid and sustained than that on the α-subunit. In animal models, T3 also decreases the number of TRH receptors in the thyrotroph.

At the hypothalamus, T4 and T3 exert feedback inhibition on TRH secretion, due mainly to decreased transcription of TRH mRNA. This effect is mediated by the thyroid hormone receptor (TRβ2) . The deiodination of T4 to T3 does not appear to take place in the TRH neurons themselves, which lack the D2 iodinase, but possibly in nearby glial cells.

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في مستشفى الكفيل.. نجاح تداخل جراحي لمريضة تعاني من اعوجاج في العمود الفقري

تزامنًا مع أيام الشهر المعظم.. المجمع العلمي يقيم أنشطة قرآنية في بابل والمثنى

الهيأة العليا لإحياء التراث تنهي استعداداتها لإقامة المؤتمر التمهيدي الأول لإحياء ألفية حوزة النجف الأشرف

قسم صناعة الشبابيك يواصل أعمال إدامة الشباك السابق لمرقد الإمامين العسكريين (عليهما السلام)

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خبراء تغذية يكشفون "أفضل وقت لتناول الإفطار"

أطعمة تزيد فرص وفاة مرضى السرطان 60 بالمئة.. ما هي؟

اختبار ثوري جديد يكشف مبكرا عن سرطان البنكرياس

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خبير يكشف عن اقتراب العلماء من فك شفرات "لغات الحيوانات" !

دراسة تدفعك لشراء ساعة ذكية "فورا".. هذا ما تقوله عن قلبك

علماء حاصلون على "نوبل": الذكاء الاصطناعي لن يستبدل الإنسان

المزيد

مواضيع ذات صلة

Transport and Metabolism of Thyroid Hormones

−Secretion of T4 and T3 and Recycling of I

Thyroglobulin Storage, Endocytosis, and Breakdown

Thyroid Peroxidase and DUOX: Tyrosine Iodination and Coupling

Thyroglobulin

The Thyroid Epithelial Cell

Introduction to Thyroid Hormones

 Regulation of Calcemia and Calcium- Phosphorus Homeostasis

Biological Actions of Parathormone (PTH)

Synthesis, Secretion, Metabolism, and Mechanism of Action of Parathormone (PTH)

Regulation of Thyroid Hormone Secretion and TSH

Biosynthesis and Secretion of Thyroid Hormones