physiology thyroid hormone

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PHYSIOLOGY THYROID HORMONE

PHYSIOLOGY THYROID HORMONE byKarishma R. PandeyDept. of Basic and Clinical Physiology

OBJECTIVES

Introduction-an anatomical considerationBio-synthesis and Secretion of thyroid hormone

TransportActivation and degradation at target organ

Physiological activities at target organs

Control/ regulation of thyroid hormone

Pathophysiology & pharmacology-A snapshotTests of thyroid function

IntroductionUniquenessEasily seen and palpated

Iodine

Stored in an extracellular site

Peptide hormones - no cell-membrane receptors

Nuclear receptors.

like most peptide hormones, T4 and T3 are made as part of a larger protein

only endocrine gland easily seen and palpated

require an essential trace element, iodine, for the production of active hormone

hormone is stored in an extracellular site within a highly proteinaceous material called thyroid colloid

unlike peptide hormones, there are no cell-membrane receptors for these hormones.

Instead, like the steroid hormones, thyroid hormones act by binding to nuclear receptors and regulate the transcription of cell proteins.

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Bio-synthesis and Secretion of Thyroid HormoneIodide TransportThyroglobulin SynthesisOxidation o f IodideOrganification (lodination)CouplingStorageSecretion

Structures of Thyroid Hormone

Secretion of thyroid hormoneTransport of thyroid hormonesSignificance of protein-bound hormonesHave slow rate of clearance from the plasma (longer half life)

Protein-bound hormones serve as reservoirs, replenishing the concentration of free hormones when they are bound to target receptors or lost form the circulation.Thus buffers any acute changes in thyroid gland functions.

Reservoir function may help to ensure a relatively uniform distribution of hormones to the tissues by preventing the excessive uptake by first cells encountered

8T4T3Total conc. in plasma8 g/dl0.15 g/dl

% of bound form99.98%99.8%Free form2 ng/dl0.3 ng/dl% of free form0.02%0.2%Biological half-lifeLong (6-7days)Shorter average 2 daysThyroxine (T4) T3rT3 ThyronineDeiodinase 1 & 2 Deiodinase 3DeiodinaseDeiodinaseThyroxine CatabolismDITMITDeiodinaseConjugated in liverHydrolysed/reabsorbed/excreted

Action at target organMechanism of T34 functional intranuclear T3 receptors: 1, 2, 1 and 2; nonfunctional receptor: 2. The different forms of thyroid receptors have patterns of expression that vary by tissue and by developmental stage.

The presence of multiple forms of the thyroid hormone receptor, with tissue and stage-dependent differences in their expression, suggests an extraordinary level of complexity in the physiologic effects of thyroid hormone.

1. Effect of thyroid hormones on BMR

Extreme excess of thyroid secretion increases BMR to 60-100% above normal

Complete lack of thyroid secretion causes BMR to fall 40-50% below normal

Mechanism of increasing metabolic rate and temperature

by increasing number, size and activity of mitochondria By increasing plasma membrane Na+-K+ ATPase ActivityBy stimulating both catabolic and anabolic reactions in pathways affecting fats ,carbohydrates, and proteins

.Metabolic rateAdjust the set point for metabolic rate of the bodyIncreases BMR and body temperature

14Effects secondary to increased metabolismIncreased O2 consumption in almost all the cells exceptions are the adult brain,testes,uterus,lymph nodes,spleen,and anterior pituitary.

Nitrogen excretion is increased

Weight loss due to catabolism of endogenous protein and fat stores

Increased urinary excretion of K+, uric acid

Precipitation of vitamin deficiency syndrome due to increased need for vitamins resulting from increased metabolic rate

Positive chronotropic , inotropic and lusitropic effect.

Increases systolic BP and decreased Diastolic BP Increased Pulse pressure and mean arterial pressure remains somewhat constant2. Cardiovascular effects thyroid hormones stimulate oxygen utilization Increases resting respiratory rate, minute ventilation and the ventilatory respose to hypercapnia and hypoxia

Increase hematocrit secondary to EPO secretion

Increase dissociation of O2 from hemoglobin by increasing red cell 2,3-diphosphoglycerate (DPG).

3.Respiratory Effects4. Autonomic Nervous system

Thyroid hormones are synergistic with catecholamines in increasing the metabolic rate, heat production, heart rate ,motor activity and excitation of central nervous system

Increases the no. of adrenergic receptors5.Effects on Nervous SystemGrowth of cerebral and cerebellar cortices.Proliferation of axons and branching of dendrites, synaptogenesis, myelination,and cell migration during brain development.Enhances wakefulness, alertness, responsiveness to various stimuli.The speed and amplitude of peripheral nerve reflexes are increased.Memory, learning and intellectual capacities.

Too much induces anxiety and nervousness, constant tiredness & difficult to sleep due to excitable effect of thyroid hormone on synapse Too little thyroid hormone- the individual tends to feel mentally sluggish & extreme somnolence Increased reactivity of the neuronal synapses in the areas of the spinal cord that control muscle

6.Effects on growth and developmentPromote expression of gene for growth hormone in somatotrophs.

T3 is required for production of both growth hormone and insulin like growth factors. It is also required for action of insulin like growth factors on epiphyseal cartilage.

They stimulate linear growth of bones and endochondral ossification and maturation of epiphyseal bone centers.

7.Effects on reproductive systemRequired for normal ovarian cycle of follicular development,maturation,and ovulation, maintenance of the healthy pregnant state ,and the homologous testicular process of spermatogenesis.

Deleterious effects may be caused by alterations in the metabolism or availability of steroid hormones thyroid hormones stimulates hepatic synthesis and release of sex steroid-binding globulin.

In femaleLack of thyroid function- Menorrhagia/Polymenorrhea-Decreased libido

In hyperthyroid woman- Oligomenorrhea- Amenorrhea (occasionally)In maleLack of thyroid hormone---loss of libido

Great excessimpotence

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Control and regulation of thyroid hormonesThyroid Disease States

Disease is associated with both inadequate production and overproduction of thyroid hormones.

HyperthyroidismEffects and symptoms

Effects and symptomsHypothyroidism

Sick Euthyroid SyndromeThe relative activity of the deiodinase changes in response to physiological and pathological stimuli

The decrease in T3 production with fasting is an important adaptive response, increase in rT3 and normal TSH

Non thyroidal illness Burns Trauma, advanced cancers,CirrhosisRenal failure.FastingGlucocorticoidsFetusCertain drugs

Thyroid Function TestsTSHFT4, (T4)T3, FT3Thyroid stimulating immunoglobulin (TSI) or TSHR antibodyAntithyroid peroxidase antibodies (Anti TPO)

Thioamides:propylthiouracil, Methimazole, CarbimazoleThiocyanate (SCN )Perchlorate (ClO4 ),Site of Action of Different Antithyroid Agents

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