Intercellular communication Distant Local General properties of endocrine organs Endocrine organs (e.g. pituitary, thyroid, parathyroid, adrenal) Endocrine tissue within other organs (pancreas, gonads, kidneys, placenta) Isolated endocrine cells (DNES, APUD) Neuroendocrine cells Common developmental scheme invagination of epithelia, losing contact with the original tissue ducts absents General properties of endocrine organs • c.t. capsule + septs • Trabecules of glandular epithelium, follicles or clusters of glandular cells or • Neurosecretory cells • Capillary network - Fenestrated capillaries - Sinusoids • Merocrine secretion - not only hormones - endocrine gland is sensu lato also liver General properties of hormones • steroids - hydrophobic, intracytoplasmic or nuclear receptors (sex hormones, corticoids) • proteins and polypeptides - hydrophilic, plasma membrane receptors (insulin, pituitary hormones, PTH, ...) • aminoacids and their derivatives (adrenalin, noradrenalin, thyroxin) Chemokines, Hormones, Survival Factors Transmitters Growth Factors (e.g., IGF1) (e.g. interleukins, (e.g. TGFa, EGF) serotonin, etc.) , J-. r-l-. I Extracellular Matrix t Death factors (e.g. FasL, Tnf) Pituitary gland (gl. pituitaria) Pituitary gland (gl. pituitoria) • sphenoid bone • sella turcica • fossa hypophysial Pituitary gland (gl. pituitaria) Pituitary gland (gl. pituitaria) • adenohypophysis {pars distalis, pars tuberalis, pars intermedia) • neurohypophysis {pars nervosa) • infundibulum, eminentia mediana Pituitary gland (gl. pituitaria) • adenohypophysis - glandotropic hormones, prolactin, GH • neurohypophysis - hypothalamic hormones - ADH, oxytocin anatomical and functional association with hypothalamus capillary systems and neuroendocrine secretion . portal vessel Neurosecretory FSH Growth Prolactin and hormone (PRL) LH during axonal trasnportion maturation - capillary plexus from arteria hypophysialis inferior (branch of arteria carotis interna —> sinus cavernosus Hypophyseal portal system - parvocellular neurons e.g. in nucleus arcuatus, preopticus, paraventricularis and nuclei tuberales - axonal transport onto primary capillary plexus in eminentia mediana (from anterior and posterior superior hypophyseal arteries) —» hypophyseal portal veins —> secondary capillary plexus in adenohypophysis —> inferior hypophyseal portal veins —> vv. jugulares internae Capillary system of hypophysis ncl. paraventricularis ncl. supraopticus Tractus hypothalamo-hypophysialis secondary plexus of posterior lobe ö hypophyseal arteries anterior lobe EminentJa mediana • elevated part of tuber cinereum, ( detachment of infundibulum p. nervosa) Embryonal development of pituitary gl. Ectoderm (Rathke's pouch) Neuroectoderm of ventral wall of diencephalon -Infundibular process Forebrain Neural ectoderm Infundibular process Rathke's pouch Oral ectoderm Mesoderm' Rathke's pouch 1. Beginning formation of Rathke's pouch and infundibular process 2. Neck of Rathke's pouch constricted by growth of mesoderm 3. Rathke's pouch "pinched off" Median eminence Sphenoid sinus Pars tubcralis Infundibulum Pars nervosa Pars intermedia 4. "Pinched off" segment conforms to neural process, forming pars distalis, pars intermedia and pars tuberalis 5. Pars tuberalis encircles infundibular stalk (lateral surface view) Pars distalis 6. Mature form A = fossa B = hypothalamus C,= eminentia mediana D = adenohypophysis Adenohypophysis (anterior lobe) Chromophilic cells Acidophils Nonglandotropic - direct effect on target tissues Bazophils Glandotropic - regulation of other endocrine glands Chromophobic cells • undifferentiated cells • degranulated ("empty") chromophils • stromal cells Pituitary Gland h&e Adenohypophysis (anterior lobe) Adenohypophysis (anterior lobe) Adrenocorticotf^ic honmne^lK, TU rplk*3f 3 JKLl^ - Tu / adrenal thyroid gonads mammary • FSH cortex giands • LH • ACTH • TSH • Prolactin • Endorphins • Growth hormone Pro-opio-melanocortin (POMC) rough ER —» pre-prohormon produced by various tissues cleavage to • ACTH (target: adrenal cortex —» kortisol) • MSH (target: melanocytes - mostly in paracrine way) • lipotropin (lipolysis, steroidogenesis) • endorphins POMC 11 ■ i ■ i 11 ii ■ i Y-MSH ACTH 0-lipotropin ii 11 ■ i ii 11 ■ i ■ i a-MSH CLIP Y-lipotropin 0-endorphin (3-MSH Corticotrophs hypofunction Addison's Disease lack of negative feedback inhibition ACTH increased tropic hormone secretion: increased ACTH levels CLfSHING'S 5YNOFLOME Thfamng of acalp hair Emolianal instability Apia -Moon face Increased (soialhaif BltHbIj hump — hypflrbOPhy and hypertension 4 JDISCi1- : DISEASE PerscfMidy changes Aríorfinia. nausea, Hypsr-pigiwiiahon Cardiao jnsuifieieney, ftypotensön Adrenal •mpřiy;- ■ AiHoirmriune - Infection ■ Tumor rneíBEiBBts Diarrhea, abdommal pain Muscle weakness Adrenal: ■ turnt* i -.jií.fli oběsily $lriseoi skin Easy tagging Muscle vKSFSt"^-■ WeaKness T-hin exťeTiibeE- Diabetes ■inillirij:: destruction of adrenal gland íauto I m mune or tu bereu los Is) Corticotrophs hyperfunction Hypothalamus (-) Corticotropin Releasing Hormone (CRH) Anterior Pituitary (-) Adrenocorticotropic Hormone (ACTH) Adrenal Cortex Cor íkdI - low Cortisol FSH (folitropin), LH (lutropin) • gonadotropic cells of adenohypophysis stimulated by GnRH • glycoproteins, 30kDa • heterodimer, two noncovalent bound subunits (a/a - common for - LH, FSH, TSH, hCG, b/ß - specific) • FSH receptor (testes, ovarium, uterus) G-protein coupled receptor - glycosylated extracellular domain of 11 leucine rich repeats specific to FSH - after ligand binding, activation of G-protein and cAMP signaling - alternative activation of MAPK cascade (ERK) - complex signaling response (prostaglandins, PLPc, NO) FSH LH ovarium follicle development (FSHR in m. granulosa ovulation, development of cells) corpus luteum, production of androgens in thecal cells testes spermatogenesis, FSHR in Sertoli cells production of testosterone in Leydig cells (expression of LHR) extragonadal FSHR in secretory endometrium of luteal phase uterus, seminal vesicles, uterus (endometrial functions, embryo- prostate, skin... unknown endometrial interactions) function TSH, thyrotropin thyrotropic cells of adenohypophysis stimulated by TRH production of T4 (thyroxin) a T3 (triiodothyronin) by thyroid gland glycoprotein, 28,5 kDa, heterodimer, two noncovalent bound subunits (a, b) TSH receptor on thyroid follicular cells G-protein signaling —» adenylylcyklase —> cAMP cAMP —» iodide channels (pendrin), transcription of thyreoglobulin, endo- and exocytic pathway cross-reactivity with hCG —> in pregnancy - alterations in synthesis of thyroid hormones (gestational hyperthyroidism) GH, somatotropin, growth hormone somatotropic cells of adenohypophysis stimulated by GHRH (somatocrinin) several molecular isoforms (alternative splicing), ~20-24 kDa broad spectrum of target cell types and physiological circuits transcription of DNA, translation of RNA, proteosynthesis lipid use (fatty acid mobilization, conversion to acetyl-CoA) inhibition of direct use of glucose, stimulation of glukoneogenesis transmembrane transport of aminoacids proteosynthesis in chondrocytes and osteoblasts, proliferation, osteogenesis GHR in various tissues RTK, JAK-STAT Pituitary gland somatomedins small proteins (MW 7,5 kDa), IGF-like produced by liver various pathologies associated with GH Muscle Bone growth Growth hormone (GH) GHRH (GH-releasing hormone) stimulates the release of GH. GHIN (GH-inhibiting hormone) inhibits the release of GH. Adipocytes break down triglycerides. The liver breaks down glycogen. Insulin-like growth factors (IGFs) stimulate amino acid uptake by target cells, promoting protein synthesis. Table 2. Nor classical Anterior Pituitary Substances and Cell(s) of Origin Substances Cell Types PEPTIDES ACTIVIN B, INHIBIN, FOLLISTATIN F,G ALDOSTERONE STIMULATING FACTOR UN ANGIOTENSIN II (ANGIOTENSINOGEN, ANGIOTENSIN 1 CONVERTING ENZYME, CATHEPSIN B, RENIN) C,G,L,S ATRIAL NATU RET IC PEPTIDE G CORTICOTROPIN-RELEASING HORMONE-BINDING PROTEIN C DYNORPHIN G GALANIN L.S.T GAWK (CHROMOGRANIN B) G GROWTH HORMONE RELEASING HORMONE UN HISTIDYL PROLINE DIKETOPIPERAZINE UN MOTILIN S NEUROMEDIN B T NEUROMEDIN U C NEUROPEPTIDE Y T NEUROTENSIN UN PROTEIN 7B2 G.T SOMATOSTATIN 28 UN SUBSTANCE P (SUBSTANCE K) G.L.T THYROTROPIN RELEASING HORMONE G. L.S.T VASOACTIVE INTESTINAL POLTPEPTIDE G,L,T GROWTH FACTORS BASIC FIBROBLAST GROWTH FACTOR C,F CHONDROCYTE GROWTH FACTOR UN EPIDERMAL GROWTH FACTOR G.T INSULIN-LIKE GROWTH FACTOR 1 S,F NERVE GROWTH FACTOR UN PITUITARY CYTOTROPIC FACTOR UN TRANSFORMING GROWTH FACTOR ALPHA L,S,G VASCULAR ENDOTHELIAL GROWTH FACTOR F CYTOKINES INTERLEUKIN-1 BETA T INTERLEUKIN-6 F LEUKEMIA INHIBITORY FACTOR C.F NEUROTRANSMITTERS ACETYLCHOLINE OL NITRIC OXIDE F C = corticotropin, F = folliculostellate cell, G = gonadotroph, L = lactotroph, S = somatotroph, T = thyrotroph, UN = unknown Clinical links Hypophyseal tumors • compression of surrounding structures (optic chiasma) • hyperfunction of endocrine component - prolactinoma - galactorrhea - hypogonadism (alterations of GnRH) - gigantism - acromegaly - nanism Afferent nerves to hypothalamus Hypothalamic neuron to posterior lohe I'araventrk ular nu< leus Hypothalamic neurons for releasing and inhibitory factors to anterior lobe Suprao|)tic nucleus Primary capillary plexus receives neurosecretions from hypothalamus Hypophyseal portal veins carry neurosecretions to anterior lobe Specific glandular cells of anterior lobe Anterior lobe Skin (melanocytes) Diabetogenic "actor tissue Thyroid hormones hormone \drenocortical 1 Estrogen Bone, muscle. Cgppancreas % N organs (growthi Oy * ' 0 's Testosterone Progesterone Posterior hypophysis (neurohypohysis) Monocellular neuron nonmyelinated nerve fibers - axons of neurosecretory cells (c.a 100 000) of hypothalamic nuclei (n. supraopticus and paraventricularis) pituicytes (neuroglia) - astrocyte-like (intermediate fialmets, GFAP) - local control of secretion from neuroscretory termini - Herring bodies - neurosecretory endings - dilatation close to capillaries Hormones - oxytocin (OT) - antidiuretic hormone (ADH, vasopresin) N^urösecrerar-jr cells Hypophyseal portal □ neu lad on Anterior pituitary hormones and prolactin Hypothalamus Pituitary gland Pöitfiriör piTuirary hormones öyjrEödn and tfaiopressin Site of hormone exocytosis Efferent vein Paraventricular nucleus Supraoptic nucleus ▼ Neurosecretory Ending (posterior pituitary). Pituicyte processes Axon Capillary rnrlolhelium Neurosecretory vesicles Arterial supply to hypothalamus Hypothalamohypophyseal tract Herring bodies Anterior lobe Basal lamina ▼ Origin of ADH. ^r—~- Hyp°,halamic Unmyelinated axon Posterior lobe Fenestrated capillary Inferior hypophyseal artery Hormone Principal Action Principal Nucleus of Origin Oxytocin (OXY) Uterine contraction, milk ejection Paraventricular Anti-diuretic Water excretion in kid hormone (ADH) arteriolar constriction ney, Supraoptic Oxytocin nonapeptide magno-cellular supraoptic and paraventricular nuclei of the hypothalamus OR - G-coupled receptor Lcu .. ^ • nonapeptide • retention of water • effective in collecting duct and distal convoluted tubule (aquaporine translocations) • blood pressure regulation by affecting t. media • diabetes insipidus, hypernatremia, polyuremia lactation reflex uterine contraction social behavior Gl/ 0 H Vasopressin Anatomy Microscopic anatomy Hormones and target tissues trabecular epithelium in cords and clusters, reticular fibers sis) superior hypophyseal arteries —> primary capillary plexus chromophobes undifferentiated cells degranulated chromophilic cells stromal cells lack hormonal activity hypophy pars distalis —> hypophyseal portal veins + inferior hypophyseal ilic tropic mammotropic cells small polypeptides dopamin (PIH) 1 (PRF —> prolactin mammary gland in gravidity and lactations lobe (adeno arteries -> secondary capillary plexus —> hypophyseal portal veins —> i/i IE acidoph nonglandoi somatotropic cells somatostatin (GHIH) 1 GHRH —> somatotropin (STH) directly liver and growth plates other tissues via somatomedins Anterior Q. O adrenal cortex —> Cortisol melanocytes pars tuberalis vv. jugulares internae chromí ACTH, MSH »ophilic dotropi thyrotropic cells Dproteir TRH TSH thyroid —> thyroxin, T3 pars intermedia Rathke's cysts X! IS on gonadotropic cells glycc GnRH FSH (ICSH), LH gonads —> androgens, estrogens, progesterone o ■£ eminentia mediana —> infundibulum anterior and posterior superior hypophyseal arteries —> primary capillary plexus, fenestrated capillaries nonmyelinated axons to .v trámce pinealocytů a .'V*^ acervulus cerebri r;j5Q_Hiiri,.;- Epiphysis (c. pineale) pinealocytes star-like, modified neurons in trabecules association with fenestrated capillaries neurosecretory dilatations nonvisual photoreception (Mel) MT2 AC | PLC I I PKA - cAMP i DAG t : AC PLC I P-CREB 1 PKC f GC 1 I cGMP, cAMPJ DAG t I i PKA J PKC t 1 P-CREB Blood 'HCC0OH ^TRYPTOPHAN TRIPTOPHAN HYDROXYLASE ITPH) HH_. CHJ* jlCHjCH.r|H,NH thyroid hormones (T3, T4) • C cells —> calcitonin C.t. capsule, septs Lobes —» lobuli - follicles 5t,usrt£ir .k. i.-ri::v Laryni Follicles (50 u,m -1 mm) - separated by interstitial loose collagen c.t. - simple epithelium (flat to cubic, according to p#p$-$$p$ secretory activity) colloid Capillary network from thyroid arteries Thyroid gland - follicles Thyroid gland - follicles Follicular cells and C-cells (parafollicular) Synthesis of T3 and T4 T4 synthesis in thyroid • sodium-iodide symporter transports two Na+ and one I- across the basement • I" is moved across the apical membrane into the colloid of the follicle. • thyroperoxidase oxidises 2 1"—» l2. • thyroperoxidase iodinates the tyrosyl residues of thyroglobulin • (TSH) stimulates the endocytosis of the colloidal content • endocytic vesicles + lysosomes, lysosomal enzymes cleave T4 from the iodinated thyroglobulin • exocytosis T3 synthesis from T4 • T4 half-life in blood 6.5 days, T3 2.5 (T4 is a reservoir for T3) • deiodination by tissue specific deiodinase enzymes generates T3 thyreoglobulin tríiodothyronin T3 tetraiodothyronin (thyroxin) T4 Alternative T3 pathway C cells of thyroid Neuroendocrine cells - pale staining - epithelial basis, under basal lamina no contact with colloid - derived from neural crest - associate with ultimobranchial body, (derivative of the 4th pharyngeal pouch) Calcitonin - inhibition of osteoclasts DEVELOPMENT OF PHARYNGEAL ARCHES ECTODERM MESODERM ENDODERM Pharyngeal Arch Pharyngeal cleft: invagination of ectoderm between adjacent arches Pharyngeal pnuch: invagination of endoderm between adjacent arches 1st cleft forms external auditory meatus 2nd arch extends over 2nd, 3rd and 4th clefts Remnant of 2nd, 3rd pr4th cleft may persist as a lateral cervical cyst 1st pouch forms Eustachian tube 2nd pouch forms palatine tonsil 3rd pouch forms thymus and inferior parathyroids 4th pouch forms superior parathyroids [5th pouch / ultimobranchial body forms C-cells of the thyroid gland) © anatomymcqs.com Thyroid development p*nihyratd endodermal proliferation of pharyngeal floor hypobranchial eminence and foramen caecum bilobed civerticulum ductus thyreoglossus paratryrotrj ■il iTürrjjm Tl-iyip0cf**lcyil \**7 ttvymfc Pyrirnifjat I'.,iti-1 ' / eorfd ihymtt ttuut Thymus Cime« E«*-pj*>?r Dwxu***!*!* *t* E**t* Parathyroid gland (gl. parathyreoidea) 6 mm, 130 mg c.t. capsule and septs Capillary network Cords and clusters of glandular cells - Chief - Oxyphilic - Adipose Capsula fibrosa hlavní buňky oxyfilní buňky tukové buňky Thyroid gland Parathyroid glands Back view Glandula parathyreoidea - přehled I, (HE), objektiv 2,5* Parathyroid gland (gl. parathyreoidea) Chief - most abundant - small cells (7-lOu.m, big nucleus - mildly acidophilic - PTH - calcium metabolism Parathyroid Gla Oxyphylic - large, polyhedral, - strongly acidophilic - round nucleus - glycogen Parathyroid gland (gl. parathyreoidea) Parathyroid hormone (PTH, parathormone, parathyrin) 84 aminoacids stimulates resorption by osteoclasts enhances resorption of calcium and magnesium in distal tubules and thick ascending limb enhances absorption in the intestine (via vD3) • Jrc/ú.uoi iMUW JomwfcOfl crdMEyMMM PTH vs. calcitonin Calcitonin Q If calcium level rises above set point O Blood calcium level rises © Thyroid gland releases calcitonin High_ Homeostasis: Blood calcium Level Low PTH 0 Parathyroid glands release parathyroid hormone (PTH) 0 Blood calcium level falls If calcium level falls below set point Embryonic development of parathyroid gland • glandulae parathyroideae superiores from endoderm of 4th pharyngeal pouch • glandulae parathyroideae inferiores from dorsal process of 3th pharyngeal pouch - together with thymus descend to lower poles of thyroid • ectopic PTH gland in thymus or mediastinum Embryonic development of parathyroid gland DEVELOPMENT OF PHARYNGEAL ARCHES ECTODERM MESODERM DODERM Pharyngeal Arch 1st deft forms external auditory meatus 2nd arch extends rjver2nd, 3rd and 4th clefts Pharyngeal cleft: invagination of ectoderm between adjacent arches Pharyngeal pouch: invagination of endoderm between adjacent arches Remnant of 2nd, 3rd or 4th cleft may persist as a lateral cervical cyst 1st pouch forms Eustachian tube 2nd pouch forms pa latine tonsil 3rd pouch forms thymus and inferior parathyroids — 4th pouch forms superior parathyroids [5th pouch / ultimo branchial tody '"" forms C-cells of the thyroid gland) © anatomymcqs.com Adrenal gland (corpus suprarenale) capillary plexus Adrenal development cortex - mesoderm - mesothelium, coelomic epithelium medulla - neural crest Adrenal cortex Adrenal cortex • Zona glomerulosa (1/10) - thin layer under capsule - relatively small cells in coiled glom - not abundand lipid droplets - mineralocorticoids • Zona fasciculata (6/10) - radially arranged trabecules - lipid droplets in cytoplasm - glucocorticoids • Zona reticularis (3/10) - branched trabecules - small, acidophilic cells - lipofuscin - androgen precursors Adrenal cortex hormones • Steroids produced incortex = CORTICOSTEROIDS • Steroidogenic cells - SER, lipid droplets, mitochondria - mineralocorticoids - glucocorticoids • Aldosteron - zona glomerulosa • KortisoI -zonafasciculata • Androgens, estrogens, progesteron - zona reticularis Adrenal medulla Clusters of glandular cells in reticular c.t. - chromaffin cells - modified postganglionic neurons - ganglionic cells - capillaries, venules, nerve fibers - adrenaline and noradrenaline Neural crest origin Adrenal vascularisation capsular arteriole capsular venule arteriae suprarenales (3) —> arterial plexus in cortex under c.t. capsule —» radially oriented fenestrated sinusoid capillaries continuous with medullar capillaries —> medullar veins —> v. suprarenalis three arterial regions 1) c.t. capsule and superior parts of cortex 2) radial capillaries of cortex continuing to medulla 3) medullar capillaries from aa. perforantes cortical arteriole c.t. capsule QJt—I z. glomerulosa z. fasciculata z. reticularis medulla medullar artery capillaries of z. glomerulosa arteria perforans capillaries of z. rasciculata capillaries of z. reticularis venules of z. reticularis I I i i <-t f Stress Hypothalamus Autonomic nerve system Adrenal medulla Adrenalin* - blood pressure, vasoconstriction, heart rate... Pituitary gland ACTH Adrenal cortex rtisol glycogen lysis stabilization of glucose levels suppression of immune system Fight or Flight Adaptation, regeneration Langerhans islet of pancreas Langerhans islets of pancreas V *** ■ f f * J, % ... .Jr j V 7 Ir) • ♦ B-cells producing insulin Ab-anti insulin-Alexa Fluor A-cells producing glucagon Ab-anti glukagon -Texas Red nkyou for attention