Endocrine System

dr. Rhiza Mohammad Ishaq Sobari Physiology dept.

 Endocrine it derives from the Greek words endo (Greek ) meaning inside, within, and crinis (Greek ) for secrete. The endocrine system is an information signal system like the nervous system. Hormones are substances (chemical mediators) released from endocrine tissue into the bloodstream that attach to target tissue and allow communication among cells.

 Hormones regulate many functions of an organism, including

stimulation or inhibition of growth mood swings induction or suppression of apoptosis activation or inhibition of the immune system regulation of metabolism preparation of the body for mating, fighting, fleeing, and other activity preparation of the body for a new phase of life, such as puberty, parenting, and menopause control of the reproductive cycle hunger cravings

Endocrine Glands: Secretion and Action of Hormones

Most, if not all, tissues secrete hormones. Hormone = chemical secreted into the blood that triggers a preprogrammed response in the target cell. Neurotransmitter = chemical secreted into synaptic cleft that affects ion channels in the target cell. Neurohormone = chemical secreted by neurons into the blood.

Classification of hormones
1. By composition: a. Amino-acids derivatives,ex: epinephrine (E), norepinephrine (NE), dopamine (E, NE & dopamine are structurally similar called catecholamines) the thyroid hormones, and melatonin. b. Peptide a. Polypeptide,ex: ADH, oxytocin, prolactin b. Glycoprotein,ex: TSH, LH, FSH c. Lipid derivatives: a. Steroid hormone, ex: androgens, estrogens, progesterons, corticosteroids,calcitriol b. Eicosanoids, ex : leucotrienes, prostaglandins (paracrine factors) By polarity: a. Nonpolar (hydrophobic) soluble in lipids steroids and thyroid hormones. b. Polar (hydrophilic) soluble in water all others.

2.

Types of cell-to-cell signaling

Classic endocrine hormones travel via bloodstream to target cells; neurohormones are released via synapses and travel via the bloostream;
paracrine hormones act on adjacent cells and autocrine hormones are released and act on the cell that secreted them..

Regulation of hormone secretion

Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are:
receipt of stimulus synthesis and secretion of hormone delivery of hormone to target cell evoking target cell response degradation of hormone

Control of Endocrine Activity

The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid. Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial.

Control of Endocrine Activity

The concentration of hormone as seen by target cells is determined by three factors: Rate of production Rate of delivery Rate of degradation and elimination

Control of Endocrine Activity

Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits, as described below in more detail.

Control of Endocrine Activity

Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells - high blood flow delivers more hormone than low blood flow.

Control of Endocrine Activity

Rate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. Shutting off secretion of a hormone that has a very short half-life causes circulating hormone concentration to plummet, but if a hormone's biological half-life is long, effective concentrations persist for some time after secretion ceases.

Feedback Control of Hormone Production

Feedback loops are used extensively to regulate secretion of hormones in the hypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion

Inputs to endocrine cells

Hormone receptor
A hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell. Binding of hormones to hormone receptors often trigger the start of a biophysical signal that can lead to further signal transduction pathways, or trigger the activation or inhibition of genes. Types of Hormone Receptors
Steroid hormone receptors Peptide hormone receptors

 Hormon mengaktifasi reseptor protein,kompleks protein-g dan ,, yg inaktif akan teraktifasi,mnyebabkan disosiasi subunit dari subunit , dan protein-g,dan interaksi ini menginisiasi pnghantaran sinyal intrasel yg akan mengubah fungsi sel : aktif/inaktif

Steroid Hormones
Steroid hormones and thyroid hormone diffuse easily into their target cells Once inside, they bind and activate a specific intracellular receptor The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein This interaction prompts DNA transcription to produce mRNA The mRNA is translated into proteins, which bring about a cellular effect

Steroid Hormones

Hormon binding dgn reseptor sitoplasma/nukleus, kompleks hormon-reseptor akan berikatan dengan hormon respon element(promotor) pada DNA,menyebabkan aktifasi/inaktifasi transkripsi gen+pembentukan mRNA+sintesis protein
Figure 16..3

 ELISA : A sensitive RIA : A procedure that measures immunoassay that uses an minute amounts of a substance, enzyme linked to an antibody such as a hormone or drug, by or antigen as a marker for the quantitating the binding, or the detection of a specific protein, inhibition of binding, of a especially an antigen or radiolabeled substance to an antibody. It is often used as a antibody. diagnostic test to determine exposure to a particular infectious agent, such as the AIDS virus, by identifying antibodies present in a blood sample.

E N D O C R I N E G L A N D S

Major Hormones Where Hormone Is Produced Hormone Pituitary gland Antidiuretic hormone (vasopressin) Corticotropin (ACTH) Growth hormone Luteinizing hormone and follicle-stimulating hormone

Function Causes kidneys to retain water and, along with aldosterone, helps control blood pressure Controls the production and secretion of hormones by the adrenal glands Controls growth and development; promotes protein production Control reproductive functions, including the production of sperm and semen, egg maturation, and menstrual cycles; control male and female sexual characteristics (including hair distribution, muscle formation, skin texture and thickness, voice, and perhaps even personality traits) Causes muscles of the uterus and milk ducts in the breast to contract Starts and maintains milk production in the ductal glands of the breast (mammary glands) Stimulates the production and secretion of hormones by the thyroid gland Controls bone formation and the excretion of calcium and phosphorus Regulates the rate at which the body functions (metabolic rate) In people, function is unclear; in other species, regulates calcium balance Helps regulate salt and water balance by retaining salt and water and excreting potassium Has widespread effects throughout the body; especially has anti-inflammatory action; maintains blood sugar level, blood pressure, and muscle strength; helps control salt and water balance Has effects on bone, mood, and the immune system Stimulate the heart, lungs, blood vessels, and nervous system Raises the blood sugar level Lowers the blood sugar level; affects the processing (metabolism) of sugar, protein, and fat throughout the body Stimulates red blood cell production Controls blood pressure

Oxytocin Prolactin Thyroid-stimulating hormone Parathyroid glands Thyroid gland Parathyroid hormone Thyroid hormone Calcitonin Adrenal glands Aldosterone Cortisol

Dehydroepiandrosterone (DHEA) Epinephrine and norepinephrine Pancreas Glucagon Insulin Erythropoietin Renin

Kidneys

Ovaries

Estrogen

Controls the development of female sex characteristics and the reproductive system Prepares the lining of the uterus for implantation of a fertilized egg and readies the mammary glands to secrete milk Controls the development of male sex characteristics and the reproductive system Controls gallbladder contractions that cause bile to enter the intestine; stimulates release of digestive enzymes from the pancreas Increases insulin release from pancreas Controls growth hormone release from the pituitary gland; causes sensation of hunger Blocks the effects of insulin on muscle Controls appetite Stimulates ovaries to continue to release progesterone during early pregnancy Keep uterus receptive to fetus and placenta during pregnancy

Progesterone

Testes

Testosterone

Digestive tract

Cholecystokinin

Glucagon-like peptide Ghrelin

Adipose (fat) tissue

Resistin Leptin Chorionic gonadotropin

Placenta

Estrogen and progesterone

The Endocrine System

Consists of several glands located in various parts of the body.
Pituitary gland: a small gland located on a stalk hanging from the base of the brain. The Master Gland Primary function is to control other glands. Produces many hormones. Secretion is controlled by the hypothalamus in the base of the brain.

The Endocrine System

The Pituitary Gland is divided into 2 areas, which differ structurally and functionally each area has separate types of hormone production.
The two segments are: Posterior Pituitary: produces oxytocin and antidiuretic hormone (ADH) Anterior Pituitary: produces thyroidstimulating hormone (TSH) growth hormone (GH) adrenocorticotropin (ACTH) follicle-stimulating hormone (FSH)

The Endocrine System

luteinizing hormone (LH) prolactin Posterior Pituitary Oxytocin (the natural form of pitocin) stimulates gravid uterus causes let down of milk from the breast. ADH (vasopressin) causes the kidney to retain water.

The Endocrine System

Anterior Pituitary Primarily regulates other endocrine glands rarely a factor in endocrinological emergencies TSH stimulates the thyroid gland to release its hormones, thus metabolic rate Anterior Pituitary Growth hormone (GH) glucose usage consumption of fats as an energy source ACTH stimulates the adrenal cortex to release its hormones FSH & LH stimulates maturation & release of eggs from ovary.

The Endocrine System

The Thyroid Gland
lies in the anterior neck just below the larynyx. Two lobes, located on either side of the trachea, connected by a narrow band of tissue called the isthmus. Sacs inside the gland contain colloid Within the colloid are the thyroid hormones: thyroxine (T4) triiodothyronine (T3) When stimulated (by TSH or by cold), these are released into the circulatory system and the metabolic rate.

The Endocrine System

C cells within the thyroid produce the hormone calcitonin Calcitonin, when released, lowers the amount of calcium in the blood.

The Endocrine System

Parathyroid Glands
small, pea-shaped glands, located in the neck near the thyroid usually 4 - number can vary regulate the level of calcium in the body
produce parathyroid hormone - level of calcium in blood Hypocalcemia can result if parathyroids are removed or destroyed.

The Endocrine System

Pancreas
a key gland located in the folds of the duodenum has both endocrine and exocrine functions secretes several key digestive enzymes

Islets of Langerhans
specialized tissues in which the endocrine functions of the pancreas occurs include 3 types of cells:
alpha ( ) beta () delta ()

each secretes an important hormone.

The Endocrine System

Alpha () cells release glucagon, essential for controlling blood glucose levels. When blood glucose levels fall, cells the amount of glucagon in the blood . The surge of glucagon stimulates the liver to release glucose stores (from glycogen and additional storage sites). Also, glucagon stimulates the liver to manufacture glucose gluconeogenesis.

The Endocrine System

Insulin is rapidly broken Beta Cells () release insulin (antagonistic to down by the liver and glucagon). must be secreted constantly. Insulin the rate at which various body cells Delta Cells () produce take up glucose. Thus, somatostatin, which insulin lowers the blood inhibits both glucagon glucose level. and insulin.

The Endocrine System

Adrenal Glands
2 small glands that sit atop both kidneys. Each has 2 divisions, each with different functions. the Adrenal Medulla secretes the catecholamine hormones norepinephrine and epinephrine (closely related to the sympathetic component of the autonomic nervous system).

The adrenal cortex is composed of 3 zones: 1. Zona Glomerulosa superficial layer secretes mineralocorticoids (aldosterone) 2. Zona Fasciculata middle layer secretes glucocorticoids (cortisol) 3. Zona Reticularis deep layer secretes gluco-corticoids and sex steroids. Fetal Zone only in fetus makes DHEA for conversion to sex steroids (mostly estrogens) by the placenta.

Gonads

Testes secrete androgens; principally testosterone from Leydig cells of seminiferous tubules. Androgens control development and maintenance of sex organs and secondary sex characteristics. Ovaries secrete progesterone and estrogens; principally estradiol-17.
Estradiol is secreted from granulosa cells of the ovarian follicle. Progesterone and estradiol is secreted from the corpus luteum.

Hipothalamus & Hipofisis

dr. Rhiza Mohammad Ishaq Sobari Physiology dept.

Hipothalamus
Tidak memiliki batas tegas Bagian atas dibatasi dari daerah thalamus dgn sulcus hipothalamicus Hasilkan hormon
Growth hormon releasing hormon (GHRH) Somatostatin (inhibisi GH & TSH) Dopamin Prolactin Releasing Factor Thyrotropin releasing hormon (TRH) Corticotropin releasing hormon (CRH) Gonadotropin releasing hormon (GnRH)

Hipofisis
Kel hipofisis terletak didasar tengkorak (sella tursica/fossa pituitaria) Terdiri dari : - hipofisis anterior (adenohipofisis) - pars intermedius (jadi satu dgn dorsal hipofisis posterior) - hipofisis posterior (neurohipofisis)

Fisiologi Adenohipofisis
Mengeluarkan hormon : 1. Hormon pertumbuhan 2. Prolaktin 3. Tiroid Stimulating Hormon (TSH) 4. Adrenocorticotropic hormon (ACTH) 5. Hormon gonadotropin : - Follicle Stimulating Hormon (FSH) - Luteinizing Hormon (LH) 6. Melanocyte stimulating hormon (MSH)

Fisiologi pars intermedius

Mengeluarkan hormon MSH Terdiri 2 sub unit alfa & beta Beta MSH ~ ACTH Pd manusia dewasa rudimenter

Fisiologi Neurohipofisis
Menghasilkan hormon : - Oksitosin - Anti Diuretik Hormon (ADH/ Arginin vasopresin) Dikendalikan nuklei hipothalamus Sekresi oksitosin dikendalikan nukleus paraventrikularis Sekresi ADH dikendalikan niklei supraoptici

Stimuli nukleus paraventrikularis (oksitosin) - uterus, cervix,vagina - papilla & areola mammae Penting proses melahirkan, kontraksi miometrium, menyusui Nuleus supraoptici (ADH) Osmoreseptor peka thd perubahan kepekatan plasma

Fisiologi adenoh

Endocrine regulation in growth

The Endocrine System

A system of glands that secrete hormones

Regulate a variety of physiological processes

Travels through bloodstream to target organ, where it exerts its effects by binding to its receptor. Receptor: Membrane (Protein Hormone) Nuclear (Steroid Hormone)

Endocrine hormone:

Thyroid Hormones
Hypothalamus TRH (Thyrotropin releasing hormone) Pituitary TSH (Thyroid stimulating hormone) Thyroid T4 thyroxine T3 thyronine iodine Permissive role: Allow for normal cell function & growth Induce N retention for protein synthesis Stimulate growth H release Increases metabolic rate

Roles

Metabolic Rate

BMR heat production

Newborns Stress

Weight regulation -receptors Heart rate Brain activity, muscle activity

SNS Activity

Brain development and body growth

Stimulates GH release

Thyroid hormones (cont.)

Secreted by fetus from week 20 on

Necessary for fetal protein synthesis and brain development

Thyroid hormone deficiency

In Utero: Cretinism (Congenital hypothyroidism mental retardation, stunting) In infancy: growth delay, may CNS damage In childhood / adolescence: growth delay, skeletal maturity delay, does not CNS damage In adulthood: T3T4 deficiency obesity T3T4 excess weight loss

Hypothyroidism
Goitre: iodine deficiency No goitre: TSH deficiency

http://www.bupa.co.uk/wellness/images/factsheets/Thyroid_disease1.gif

Hyperthyroidism

http://www.bupa.co.uk/wellness/images/factsheets/Thyroid_disease2.gif

Growth Hormone
Hypothalamus Somatostatin + GHRH

Anterior pituitary gland

GH
Liver
IGF-1 Somatomedin

Adipose Tissue -lipolysis - release of FFAs Most Tissues glucose utilization - blood glucose

Cartilage and bone growth Muscle and other organs: -Protein synthesis and growth

GH levels and effects are most pronounced during puberty

Growth hormone disorders

Excess GH

Pre-puberty: gigantism

bone growth, > 7 ft. tall Some tissues still grow: cartilage in nose, hands, feet, ridges of eyebrow, chin, tongue Metabolic effects: constant increase in blood sugar, increased insulin type 2 diabetes. Can also increase muscle narrowing of arteries, heart attack

Post-puberty: acromegaly

 GH Deficiency

GH, IGF-1 Short stature Metabolic effects

Insulin

Hormone of Feasting From Pancreas - cells from Islets of Langerhans Allows glucose to enter the cell

Energy Metabolic Processes

glucose uptake into tissues Affects glucose transporter

Growth

Glycogen synthesis Fat synthesis Protein synthesis

Children with poorly controlled Type I diabetes often have short stature

Glucagon Hormone of Fasting

Insulin Deficiency

Lipolysis

FFA ketone bodies acidifies blood

Protein breakdown Plasma Glucose

Osmotic diuresis

water excretion plasma volume arterial blood pressure brain blood flow

Androgens and Estrogens

Produced in gonads (ovaries, testes) and adrenal glands, in puberty

Androgens

Will fuse epiphysis and stop linear growth - earlier puberty in women contributes to their shorter stature

Primarily DHEA (dihydroepiandrosterone) Converted to estrogens, testosterone in tissues Peaks in young adults Secondary sex characteristics In women: DHEA stimulates growth in adolescence, e.g. muscle, bone Important during fetal period and during menopause

Estrogen
During puberty: 2 sex characteristics Promotes growth of uterus Stabilizes blood cells in skin Bone strength

Gangguan fungsi hipofisis

Panhipopituitarisme kekurangan hormon :
GH, TSH, ACTH, Gonadotropin,Prolaktin

Gejala sesuai kekurangan hormon Etiologi :infeksi,iskemia,neoplasma, granuloma,aneurisma dll

 Akromegali / gigantisme Hipersekresi GH / HP Sesudah epifises menutup : akromegali Sebelum epifises menutup : gigantisme Akibat tumor hipofisis Gejala : Bentuk muka berubah, pertumbuhan gigi tak teratur, kiposis, atropati, pertumbuhan tulang ekstremitas berlebihan

 Pembesaran dan penebalan hidung, lidah, bibir, telinga, tangan dan kaki Kulit menebal, basah dan beminyak, lipatan kulit kasar dan melebar, penebalan telapak kaki Suara parau Pada metabolisme : intoleransi glukosa, hiperfosfatemia, hiperlipidemia dan hiperkalsemia, osteoporosis.

 Gambaran klinis akibat tumor - Pembesaran keatas : sakit kepala, ggn penglihatan - Pembesaran ke lateral : kelumpuhan syaraf III,IV,V dan VI - Penyumbatan pemb darah lokal - Pertumbuhan ke inferior : CSF rinorea - Pertumbuhan ke anterior : perubahan kepribadian - Infark

Gangguan Pertumbuhan
Defisiensi hormon pertumbuhan Manifestasi perawakan pendek (shurt stature) Etiologi perawakan pendek Defek intrinsik : displasia tulang,kelainan kromosom, kecebolan primordial Lingkungan : ggn gizi,gagal ginjal kronik, penyakit darah dll Hormonal : defisiensi HP, defisiensi tiroid, kelebihan glukokortikoid

Gangguan pertumbuhan
Gambaran klinis HP << perawakan pendek berat (cebol), agak gemuk, lemak subcutan di abdomen bertambah, hipoglikemia, proporsi tulang normal,pematangan tulang terlambat.