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Molecular Endocrinology: Thyroid System, Lecture notes of English Language

A detailed overview of the thyroid system, including the structure and function of the thyroid gland, the synthesis and secretion of thyroid hormones (t4 and t3), the role of the hypothalamus-pituitary-thyroid (hpt) axis in regulating thyroid function, and the mechanisms by which thyroid-stimulating hormone (tsh) stimulates thyroid cell functions. Topics such as the transport of iodides, the synthesis and storage of thyroglobulin, the release of thyroid hormones, the transport of thyroid hormones in the blood, and the peripheral conversion of t4 to t3. It also discusses the two main signal transduction pathways (camp and phospholipase-c) involved in the effects of tsh on thyroid cells. This comprehensive information on the molecular endocrinology of the thyroid system could be valuable for students studying endocrinology, physiology, or related fields.

Typology: Lecture notes

2021/2022

Uploaded on 11/04/2022

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Instructor:
Office hour: By appointment
Class website: HuskyCT
Class Meeting Time: Tue/Thu 12:3 0 p.m . to 1:45 p.m.
Class Meeting Place: TLS 111
Dr. Jianzhong Yu
Office: PBB 110A
Tel: 8 60-486-5440
E-mail: Jianzhong.yu@uconn.edu
PNB 3270/5270
MOLECULAR ENDOCRINOLOGY
Part II
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Instructor:

Office hour: By appointment

Class website: HuskyCT

Class Meeting Time: Tue/Thu 12:30 p.m. to 1:45 p.m.

Class Meeting Place: TLS 111

Dr. Jianzhong Yu Office: PBB 110A Tel: 860- 486 - 5440 E-mail: Jianzhong.yu@uconn.edu PNB 3270/ MOLECULAR ENDOCRINOLOGY Part II

Date Topics 10/18 Tue Hypothalamus-pituitary-thyroid 10/20 Thu Hypothalamus-pituitary-thyroid 10/25 Tue Hypothalamus-pituitary-adrenal gland 10/27 Thu Hypothalamus-pituitary-adrenal gland 11/01 Tue Hypothalamus-pituitary-adrenal gland 11/03 Thu Growth Hormone 11/08 Tue Growth Hormone 11/10 Thu Insulin and Diabetes 11/15 Tue Insulin and Diabetes 11/17 Thu Insulin and Diabetes 11/22 Tue Thanksgiving Recess 11/24 Thu Thanksgiving Recess 11/29 Tue Bioregulation of calcium and phosphate 12/01 Thu Review session 12/06 Tue Exam 2 12/08 Thu Graduate student presentation

v Hypothalamus-pituitary-thyroid (HPT) axis

v Hypothalamus-pituitary-adrenal (HPA) axis

v Hypothalamus-pituitary-hepatic (HPH) or liver axis

v Hypothalamus-pituitary-gonad (HPG) axis

Four Major Hypothalamus-Pituitary (HP) Axes

MOLECULAR ENDOCRINOLOGY Thyroid System– I

v About 93% of the metabolically

active hormones secreted by the

thyroid gland is T4, and about 7%

T3.

v T3 is responsible for most of tissue

actions.

v Almost all T4 is eventually

converted to T3 in the tissues.

v T3 is about 4 times potent than T4.

Thyroid Metabolic Hormones

Synthesis and Secretion of Thyroid Hormones

(T4, T3) (calcitonin) v The thyroid gland is composed of closely packed spherical units termed follicles, which are invested with a rich capillary network. v The interior of the follicle is filled with the clear proteinaceous colloid that normally is the major constituent of the total thyroid mass. v The major constituent of colloid is the large glycoprotein thyroglobulin , which contains the thyroid hormones with its molecule.

Synthesis and Secretion of Thyroid Hormones

v To form normal quantities of T4, about 50 milligrams of ingested iodine in the form of iodides are required each year, or about 1 mg/week.

Synthesis and Secretion of Thyroid Hormones

v To form normal quantities of T4, about 50 milligrams of ingested iodine in the form of iodides are required each year, or about 1 mg/week. v Iodides ingested orally are absorbed from the gastrointestinal tract into the blood in about the same manner as chlorides. v Most of the iodides are rapidly excreted by the kidneys. Only about 1/5 are selectively removed from the circulating blood by the cells of the thyroid gland and used for synthesis of the thyroid hormones.

Synthesis and Secretion of Thyroglobulin

Ø Thyroglobulin is synthesized in endoplasmic reticulum and packaged into secretary granules in Golgi of the follicle cells.

v Synthesis and secretion of Thyroglobulin (Tg), a 660

kDa, dimeric glycoprotein produced by the follicular

cells.

Ø Each molecule of thyroglobulin contains about 100 - 120 tyrosine amino acids, and they are the major substrates that combine with iodine to form the thyroid hormones.

Synthesis of Thyroid Hormones

Release of Thyroid Hormones

v Thyroglobulin itself is not released into the circulating blood in measurable amounts; instead, T4 and T3 must first be cleaved from the thyroglobulin molecule, and then these free hormones are released.

Release of Thyroid Hormones

Ø About three quarters (3/4) of the iodinated tyrosine in the thyroglobulin never becomes thyroid hormones but remains MIT & DIT. Ø During the digestion of the thyroglobulin molecule to release T4 and T3 into the blood, these iodinated tyrosine (MIT & DIT) are also freed from the thyroglobulin molecules but are not secreted into the blood. Ø Instead, their iodine is cleaved by a deiodinase enzyme that makes all this iodine available again for recycling within the gland for forming additional thyroid hormones. Ø In the congenital absence of this deiodinase enzyme, many persons become iodine deficient because of failure of this recycling process.

v Approximately 80% of T3 is derived from the peripheral tissues by

the enzymatic removal of a single 5ʹ iodine atom from T4.

v Deiodinase enzymes are essential control points of cellular

thyroid activity that determine intracellular activation and

deactivation of thyroid hormones.

Peripheral Thyroid Hormone Conversion

Ø Type I deiodinase (D1) and type II deiodinase (D2): q Increase cellular thyroid activity by converting inactive thyroxine (T4) to the active triiodothyronine (T3) Ø Type III deiodinase (D3): q Reduces cellular thyroid activity by converting T4 to the anti-thyroid reverse T (reverse T3): metabolically inactive form of T3; bind to a cell in the same way T does; will compete for receptors

Control of cellular thyroid levels is mediated through three different

deiodinase enzymes present in different tissues in the body:

Peripheral Thyroid Hormone Conversion