Principles of Principles of EndocrinologyEndocrinology

Department of Endocrinology

First Affiliated HospitalSun Yet-sen University

Cao Xiaopei

Principles of EndocrinologyPrinciples of Endocrinology

Glands

Hormones

EndocrineEndocrine

hormones from specialized cells hormones from specialized cells in glands or tissue are in glands or tissue are secrected and transported in secrected and transported in the blood to a distant site of the blood to a distant site of action(classic “endocrine” action(classic “endocrine” effect), or act directly upon effect), or act directly upon nearby cells which is called nearby cells which is called “paracrine” activity. “paracrine” activity.

ExocrineExocrine

products from glands are products from glands are secrected externally or secrected externally or into a lumen, such as the into a lumen, such as the gastrointestinal tract.gastrointestinal tract.

Endocrine SystemEndocrine System

Elements of endocrine system:Elements of endocrine system: Endocrine organsEndocrine organs APUD system APUD system Hormonal secrentory cells Hormonal secrentory cells

Major endocrine organs and common endocrine Major endocrine organs and common endocrine problemsproblems

OOther endocrine ther endocrine sites sites Islet ： insulin （ βcell ）、 glucagon （ αcel

l ） somatostatin 、 VIP…

Mucosa in GI tract ：gastrin 、 cholecystokinin 、 secretin 、 VIP…

Kidney: 1,25-(OH)2D3, Renin ， EP ， PG…

Lung ： APUD…

Heart ： natriuretic peptide…

Endothelial cell ： endothelin…

HormoneHormone

Chemical messengers produced Chemical messengers produced by a variety of specialized by a variety of specialized secretory cellssecretory cells

Chemical signals secreted into Chemical signals secreted into the blood stream that act on the blood stream that act on distant tissues, usually in a distant tissues, usually in a regulatory fashionregulatory fashion

Sources of HormonesSources of Hormones

Hormone secretory cells Hormone secretory cells (found around human body) (found around human body)

Endocrine glandsEndocrine glands Tissues or cells of endocrine Tissues or cells of endocrine

function:function:neurosecretory celneurosecretory cells in hypothalamus, ls in hypothalamus, hormone secretory cells/organ cells hormone secretory cells/organ cells with endocrine function in GI tract, with endocrine function in GI tract, kidney, heart, lung, etckidney, heart, lung, etc

Hormones involved in Hypothalamus-Pituitary axis and Hormones involved in Hypothalamus-Pituitary axis and their functiontheir function

Classification of HormoneClassification of Hormone

Amino acid derivatives: dopamine, Amino acid derivatives: dopamine, catecholamines, thyroid hormone(TH)catecholamines, thyroid hormone(TH)

Small neuropeptides: gonadotropin-Small neuropeptides: gonadotropin-releasing hormone(GnRH), thyrotropin-releasing hormone(GnRH), thyrotropin-releasing hormone(TRH), somatostatin, releasing hormone(TRH), somatostatin, vasoprssinvasoprssin

Large proteins: insulin, luteinizing Large proteins: insulin, luteinizing hormone(LH), parathyroid hormone(PTH)hormone(LH), parathyroid hormone(PTH)

Steroid hormones: cortisol, estrogenSteroid hormones: cortisol, estrogen Vitamin derivatives: retinoid(VitA), Vitamin derivatives: retinoid(VitA),

vitamin D, a variety of peptide growth vitamin D, a variety of peptide growth factorsfactors

Synthesis, Storage and Release Synthesis, Storage and Release of Hormonesof Hormones

Peptide hormones: Peptide hormones:

Neural or endocrine stimulationNeural or endocrine stimulation → → transcription from DNAtranscription from DNA → mRNA → → mRNA → peptide productpeptide product → → posttranslational posttranslational protein processingprotein processing → → intracellular sorting, intracellular sorting, membrane integrationmembrane integration → → storage or storage or secretionsecretion. .

Synthesis and Processing of Synthesis and Processing of

InsulinInsulin

Synthesis, Storage and Synthesis, Storage and Release of HormonesRelease of Hormones

Steroid hormone:Steroid hormone:

Synthesis of most steroid hormones Synthesis of most steroid hormones is based on modifications of the is based on modifications of the precursor and cholesterol. precursor and cholesterol.

Multiple regulated enzymatic steps Multiple regulated enzymatic steps are required for the synthesis of are required for the synthesis of testosterone, estradiol, cortisol and testosterone, estradiol, cortisol and vitamin D . vitamin D .

Patterns of secretionPatterns of secretion

Hormone secretion is continuous(e.g. Hormone secretion is continuous(e.g. thyroid hormone) or intermittent(e.g. thyroid hormone) or intermittent(e.g. LH,FSH).LH,FSH).

Biological rhythms ------ CircadianBiological rhythms ------ Circadian Circadian means changes over the 24 Circadian means changes over the 24

hours of the day-night cycle and is best hours of the day-night cycle and is best shown for the pituitary-adrenal axis.shown for the pituitary-adrenal axis.

Plasma cortisol levels during a 24-Plasma cortisol levels during a 24-

hour periodhour period

Hormonal and follicular changes during Hormonal and follicular changes during the normal menstrual cyclethe normal menstrual cycle

The menstrual The menstrual cycle is the cycle is the best example best example of a longer and of a longer and more complex more complex (28-day) (28-day) biological biological rhythm. rhythm.

Patterns of secretionPatterns of secretion

Clinical significance of recognising Clinical significance of recognising rhythms of hormonal secretion:rhythms of hormonal secretion:

1. 1. Testing the hormone Testing the hormone

concentrationconcentration

2. 2. Hormonal replacement therapyHormonal replacement therapy

Patterns of secretionPatterns of secretion

Other regulatory factorsOther regulatory factors StressStress SleepSleep Feeding and fastingFeeding and fasting

Plasma Transport of Plasma Transport of HormonesHormones

HormoneHormone Binding protein(s)Binding protein(s)Thyroxine (T4)Thyroxine (T4) Thyroxine-binding globulin Thyroxine-binding globulin

(TBG)(TBG)

Thyroxine-binding prealbumin Thyroxine-binding prealbumin (TBPA) (TBPA)

AlbuminAlbumin

Triiodothyronine Triiodothyronine (T3) (less bound (T3) (less bound than T4)than T4)

Thyroxine-binding globulin Thyroxine-binding globulin (TBG)(TBG)Albumin Albumin

Testosterone, Testosterone, estradiol estradiol

Sex hormone-binding globulin Sex hormone-binding globulin (SHBG) (SHBG)

Insulin-like growth Insulin-like growth factor-I (IGF-l) factor-I (IGF-l)

IGF-binding proteins (mainly IGF-binding proteins (mainly IGF-BP3) IGF-BP3)

Cortisol Cortisol Cortisol-binding globulin Cortisol-binding globulin (CBG) (CBG)

Hormones ,their receptors and pathwaysHormones ,their receptors and pathways

Degradation of Degradation of HormonesHormones

Hormone transport and degradation Hormone transport and degradation dictate the rapidity with which a dictate the rapidity with which a hormonal signal decays. Some hormonal signal decays. Some hormonal signals are evanescent hormonal signals are evanescent (e.g.somatostatin), whereas others (e.g.somatostatin), whereas others are longer lived (e.g. TSH)are longer lived (e.g. TSH)

Most hormones are deactivated in Most hormones are deactivated in live, kidney or peripheral tissues. live, kidney or peripheral tissues. Thus it must be noted that hepatic Thus it must be noted that hepatic insufficiency or renal insufficiency may insufficiency or renal insufficiency may result in prolonged half life of some result in prolonged half life of some hormoneshormones

Metabolism Metabolism

organ functionorgan function

growth growth

development reproduction development reproduction

Maintainance of homostasis of Maintainance of homostasis of

internal enviromentinternal enviroment

Functions of HormonesFunctions of Hormones

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Hypothalamus Pituitary-target gland axis

Hypothalamus Pituitary thyroid axis

Hypothalamus Pituitary adrenal axis

Hypothalamus Pituitary gonad axis

Endocrine and metabolism

Insulin vs glucose

PTH vs calcium

ADH vs plasma osmotic pressure

Hypothalamus Pituitary Hypothalamus Pituitary thyroid axisthyroid axis

Hypothalamus Pituitary Hypothalamus Pituitary adrenals axisadrenals axis

Hypothalamus Pituitary gonad Hypothalamus Pituitary gonad axisaxis

Insulin and blood glucoseInsulin and blood glucose

Classification of endocrine Classification of endocrine diseasedisease

1. primary endocrine disorder

2. secondary to other disease

3. ectopic endocrine disorder

4. due to receptor dysfunction

5. heredity abnormal hormones

6. iatrogenic

Clinical picturehistory 、 symptom 、 signLab findings evidence of metabolic disturbance: target tissue or/and organs function

evidence of inappropriate hormone ： hormones or their metabolite of

endocrine function test immunology

Diagnosis

ImageologyX ray ， CT ， B

ultrasound ， isotope

Histology and cytology

Cytogenetics

Diagnosis

Typical features in endocrine disease

dwarfism

gigantism

acromegaly

Typical features in endocrine disease

Cushing

syndrome

hyperthyroidism

Cretinism

Addison

disease

Principal of Principal of diagnosisdiagnosis functional Cushing’s symdrome pathology adrenal hyperplasia etiology pituitary microadenoma complications diabetes diabetic nephropathy concurrent disease hypertension cataract

prophylaxis ： endemic goiter Iodine deficiencyiodine replacement

Treatment ： hyperfunctioning medicine 、 surgery 、 radiation hypofunction hormones replacement and

transplantation symptomatic and supporting therapy

prophylaxis and prophylaxis and treatmenttreatment

Thank you for your attentionThank you for your attention!!