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Principles of Endocrinology Department of Endocrinology First Affiliated Hospital Sun Yet-sen University Cao Xiaopei Principles of Endocrinology Glands Hormones Endocrine hormones from specialized cells in glands or tissue are secrected and transported in the blood to a distant site of action(classic “endocrine” effect), or act directly upon nearby cells which is called “paracrine” activity. Exocrine products from glands are secrected externally or into a lumen, such as the gastrointestinal tract. Endocrine System Elements of endocrine system: Endocrine organs APUD system Hormonal secrentory cells Major endocrine organs and common endocrine problems Other endocrine sites Islet:insulin(βcell)、glucagon(αcell) 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… Hormone Chemical messengers produced by a variety of specialized secretory cells Chemical signals secreted into the blood stream that act on distant tissues, usually in a regulatory fashion Sources of Hormones Hormone secretory cells (found around human body) Endocrine glands Tissues or cells of endocrine function: neurosecretory cells in hypothalamus, hormone secretory cells/organ cells with endocrine function in GI tract, kidney, heart, lung, etc Hormones involved in Hypothalamus-Pituitary axis and their function Classification of Hormone Amino acid derivatives: dopamine, catecholamines, thyroid hormone(TH) Small neuropeptides: gonadotropin-releasing hormone(GnRH), thyrotropin-releasing hormone(TRH), somatostatin, vasoprssin Large proteins: insulin, luteinizing hormone(LH), parathyroid hormone(PTH) Steroid hormones: cortisol, estrogen Vitamin derivatives: retinoid(VitA), vitamin D, a variety of peptide growth factors Synthesis, Storage and Release of Hormones Peptide hormones: Neural or endocrine stimulation → transcription from DNA → mRNA → peptide product → posttranslational protein processing → intracellular sorting, membrane integration → storage or secretion. Synthesis and Processing of Insulin Synthesis, Storage and Release of Hormones Steroid hormone: Synthesis of most steroid hormones is based on modifications of the precursor and cholesterol. Multiple regulated enzymatic steps are required for the synthesis of testosterone, estradiol, cortisol and vitamin D . Patterns of secretion Hormone secretion is continuous(e.g. thyroid hormone) or intermittent(e.g. LH,FSH). Biological rhythms ------ Circadian Circadian means changes over the 24 hours of the day-night cycle and is best shown for the pituitary-adrenal axis. Plasma cortisol levels during a 24-hour period Hormonal and follicular changes during the normal menstrual cycle The menstrual cycle is the best example of a longer and more complex (28-day) biological rhythm. Patterns of secretion Clinical significance of recognising rhythms of hormonal secretion: 1. Testing the hormone concentration 2. Hormonal replacement therapy Patterns of secretion Other regulatory factors Stress Sleep Feeding and fasting Plasma Transport of Hormones Hormone Binding protein(s) Thyroxine (T4) Thyroxine-binding globulin (TBG) Thyroxine-binding prealbumin (TBPA) Albumin Triiodothyronine (T3) (less bound than T4) Thyroxine-binding globulin (TBG) Albumin Testosterone, estradiol Sex hormone-binding globulin (SHBG) Insulin-like growth factor-I (IGF-l) IGF-binding proteins (mainly IGF-BP3) Cortisol Cortisol-binding globulin (CBG) Hormones ,their receptors and pathways Degradation of Hormones Hormone transport and degradation dictate the rapidity with which a hormonal signal decays. Some hormonal signals are evanescent (e.g.somatostatin), whereas others are longer lived (e.g. TSH) Most hormones are deactivated in live, kidney or peripheral tissues. Thus it must be noted that hepatic insufficiency or renal insufficiency may result in prolonged half life of some hormones Functions of Hormones Metabolism organ function growth development reproduction Maintainance of homostasis of internal enviroment Feedback 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 thyroid axis Hypothalamus Pituitary adrenals axis Hypothalamus Pituitary gonad axis Insulin and blood glucose Classification of endocrine disease 1. primary endocrine disorder 2. secondary to other disease 3. ectopic endocrine disorder 4. due to receptor dysfunction 5. heredity abnormal hormones 6. iatrogenic Diagnosis Clinical picture history、symptom、sign Lab 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 Imageology X ray,CT,B ultrasound ,isotope Histology and cytology Cytogenetics Typical features in endocrine disease dwarfism acromegaly gigantism Typical features in endocrine disease Addison disease hyperthyroidism Cushing syndrome Cretinism Principal of diagnosis functional Cushing’s symdrome pathology adrenal hyperplasia etiology pituitary microadenoma complications diabetes diabetic nephropathy concurrent disease hypertension cataract prophylaxis and treatment prophylaxis: endemic goiter Iodine deficiencyiodine replacement Treatment: hyperfunctioning medicine、surgery、radiation hypofunction hormones replacement and transplantation symptomatic and supporting therapy Thank you for your attention!