ΟΙ ΚΛΑΣΣΙΚΟΙ ΕΝΔΟΚΡΙΝΕΙΣ ΑΔΕΝΕΣ ΟΡΓΑΝΑ ΜΕ ΕΝΔΟΚΡΙΝΕΙΣ ΛΕΙΤΟΥΡΓΙΕΣ

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2 FIGURE 1.1 Chemical communication between cells. A: Local. Secretors product, shown as red dots, reaches nearby target cell by diffusion through extracellular fluid (paracrine or autocrine communication). Juxtacrine: Communication by physical contact via signaling molecules in the membrane of one cell activating membrane receptor molecules in an adjacent cell. B: Endocrine. Secretory product reaches distant cells by transport through the circulation. C: Secretory product released from terminals of long cell processes reaches target cells distant from the nerve cell body by diffusion across the synaptic cleft.

3 ΟΙ ΚΛΑΣΣΙΚΟΙ ΕΝΔΟΚΡΙΝΕΙΣ ΑΔΕΝΕΣ ΥΠΟΦΥΣΗ ΘΥΡΕΟΕΙΔΗΣ ΠΑΡΑΘΥΡΕΟΕΙΔΕΙΣ ΑΔΕΝΕΣ ΠΑΓΚΡΕΑΣ (ΝΗΣΙΔΙΑ ΤΟΥ LANGERHANS) ΕΠΙΝΕΦΡΙΔΙΑ ΓΟΝΑΔΕΣ (ΟΡΧΕΙΣ & ΟΩΘΗΚΕΣ) ΠΛΑΚΟΥΝΤΑΣ ΟΡΓΑΝΑ ΜΕ ΕΝΔΟΚΡΙΝΕΙΣ ΛΕΙΤΟΥΡΓΙΕΣ ΕΓΚΕΦΑΛΟΣ ΚΑΡΔΙΑ ΗΠΑΡ ΓΑΣΤΡΕΝΤΕΡΙΚΟ ΣΥΣΤΗΜΑ ΝΕΦΡΟΙ ΛΙΠΩΔΗΣ ΙΣΤΟΣ

4 Επίπεδο του όλου σώματος Ρύθμιση και ολοκλήρωση 1ισορροπίας των ιόντων και των υγρών του σώματος, 2ομοιόστασης της ενέργειας (μεταβολισμός), 3αντιμετώπισης των μεταβολών του περιβάλλοντος, 4αύξησης και ανάπτυξης, 5αναπαραγωγής. Δράσεις των Ορμονών Μοριακό Επίπεδο Ρύθμιση 1 Μεταγραφής των γονιδίων, 2 Πρωτεινοσύνθεσης, 3 Αποικοδόμησης, 4 Ενζυμικής δραστηριότητας, 5 Διαμόρφωσης πρωτεϊνών, 6 Αλληλεπιδράσεων πρωτεϊνών πρωτεϊνών. Κυτταρικό επίπεδο Ρύθμιση 1 Κυτταρικής διαίρεσης, 2 Διαφοροποίησης και Θανάτου των κυττάρων (απόπτωση), 3 Κινητικότητας, 4 Έκκρισης, 5 Πρόσληψης των θρεπτικών συστατικών.

5 ΧΗΜΙΚΗ ΦΥΣΗ ΤΩΝ ΚΛΑΣΣΙΚΩΝ ΟΡΜΟΝΩΝ Παράγωγα Τυροσίνης Επινεφρίνη Νορεπινεφρίνη Ντοπαμίνη Τριϊωδοθυρονίνη Θυροξίνη Στεροειδή Τετοστερόνη Οιστραδιόλη Προγεστερόνη Κορτιζόλη Αλδοστερόνη Βιταμίνη D Πεπτίδια ( 20 αμινοξέα) Ωκυτοκίνη Αντιδιουριτική Ορμόνη Αγγειοτασίνη Διεγερτική ορμόνη των μελανινοκυττάρων Σωματοστατίνη Εκλυτική ορμόνη της θυρεοτροπίνης Γαστρίνη Χολοκυστοκινίνη Πρωτεϊνες( 20 αμινοξέα) Ινσουλίνη Γλυκαγόνη Φλοιοτρόπος ορμόνη Θυρεοτροπίνη Σεκρετίνη Ωοθυλακιοτρόπος ορμόνη Ωχρινοτρόπος ορμόνη Αυξητική ορμόνη Προλακτίνη Καλσιτονίνη κλπ

6 FIGURE 1.8 Post-translational processing. The leader sequence or signal peptide of proteins destined for secretion enters the cisternae of the endoplasmic reticulum even as peptide elongation continues. In the endoplasmic reticulum (1) the leader sequence is removed, (2) the protein is folded with the assistance of protein chaperons, (3) sulfhydryl bridges may form, and (4) carbohydrate may be added (glycosylation). The partially processed protein (5) is then entrapped in vesicles that bud off the endoplasmic reticulum and (6) fuse with the Golgi apparatus, where glycosylation is completed, and (7) the protein is packaged for export in secretory vesicles in which the final stages of processing take place.

7 FIGURE 1.9 Exocytosis. 1. Immature secretory vesicles bud off the trans-golgi stacks. 2. Maturation of the vesicle includes extrusion of some proteins and water, acidification of vesicle contents, and condensation of enclosed proteins to form dense core granules. 3. Mature vesicles residing deep in the cytosol as a reserve pool await a signal for recruitment (4) to the readily releasable pool adjacent to the plasma membrane. 5. In preparation for secretion, the vesicles become tethered to the membrane (docking). 6. An energydependent interaction forms a loose association of special proteins (SNARE proteins) in the membranes of the vesicles with counterparts in the plasma membrane, priming the vesicles to respond to a secretory stimulus. 7. Secretion is triggered by an increase in cytoplasmic calcium that produces conformational changes in the SNARE proteins that brings the membranes of the vesicles into such close apposition to the plasma membrane that fusion occurs and a secretory pore is formed. 8. Expansion of the pore as the vesicle membrane is incorporated into the plasma membrane releases vesicular contents into the extracellular fluid.

8 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

9 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

10 FIGURE 1.10 Hormone binding to plasma proteins. Bound hormone is in equilibrium with a small fraction of free unbound hormone. Only the free hormone can pass through capillary endothelium to reach target cells or sites of degradation.

11 FIGURE 1.11 Specificity of hormone signaling. Although all cells come in contact with the hormone, only the cells colored blue have receptors and therefore can respond to the hormone. (H = hormone; HR = hormone receptor)

12 Χαρακτηριστικά των υποδοχέων Οι υποδοχείς των ορμονών είναι πρωτεΐνες ή γλυκοπρωτεϊνες και: Αναγνωρίζουν την ορμόνη από άλλα μόρια που πιθανόν έχουν παρόμοιες δομές. Δεσμεύουν την ορμόνη ακόμα και όταν η συγκέντρωσή της είναι πολύ χαμηλή (10-8Μ 10-12Μ). Όταν δεσμεύεται η ορμόνη, ο υποδοχέας αλλάζει διαμόρφωση. Παίζει καταλυτικό ρόλο στα βιοχημικά γεγονότα που ακολουθούν εντός του κυττάρου.

13 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

14 FIGURE 1.13 General scheme of steroid hormone action. Steroid hormones penetrate the plasma membrane and bind to intracellular receptors in the nucleus or cytoplasm. Hormone binding activates the receptor, which forms complexes with other proteins and binds to specific acceptor sites (hormone response elements, HRE) on DNA to initiate transcription and formation of the proteins that express the hormonal response. The steroid hormone then is cleared from the cell.

15 FIGURE 1.14 Schematic view of a nuclear receptor. The zinc fingers as shown are disproportionately enlarged.

16 FIGURE 1.15 Activation of steroid hormone receptors. Inactive receptors associated with other proteins react with hormone, shed their associated proteins, and change their conformation. They can then form dimers that bind DNA and a variety of nuclear peptide regulators of gene transcription. 59 kda = a protein with a mass of 59 kilodaltons; Hsp90 = 90 kda heat shock protein; Hsp70 = 70 kda heat shock protein.

17 FIGURE 1.16 An unactivated G-protein coupled receptor. The seven transmembrane alpha helices are connected by three extracellular and three intracellular loops of varying length. The extracellular loops may be glycosylated, and the intracellular loops and C- terminal tail may be phosphorylated. The receptor is coupled to a G-protein consisting of a GDP-binding -subunit bound to a / component. The and subunits are tethered to the membrane by lipid groups. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009 by Academic Press. All rights reserved.

18 FIGURE 1.17 Activation of G-protein coupled receptor. (I) Resting state. (II) Hormone binding produces a conformational change in the receptor that causes (III) the subunit to exchange ADP for GTP, dissociate from the / subunit and interact with its effector molecule. The / -subunit also interacts with its effector molecule. (IV) The subunit converts GTP to GDP, which allows it to reassociate with the / -subunit, and the hormone dissociates from the receptor, restoring the resting state. (I). Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009 by Academic Press. All rights reserved.

19 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

20 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

21 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

22 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

23 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

24 NEYPOEΠIΣTHMH KAI ΣYMΠEPIΦOPA ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

25 FIGURE 1.23 Phosphorylation of tyrosines on dimerized receptors (R) following hormone (H) binding provides docking sites for the attachment of proteins that transduce the hormonal signal. The growth factor binding protein 2 (GRB2) binds to a phosphorylated tyrosine in the receptor, and binds at its other end to the nucleotide exchange factor SOS, which stimulates the small G-Protein Ras to exchange its GDP for GTP. Thus activated, Ras in turn activates the protein kinase Raf, which phosphorylates mitogen activated protein (MAP) kinase and initiates the MAP kinase cascade that ultimately phosphorylates nuclear transcription factors. The isoform of phospholipase C (PLC ) docks on the phosphorylated receptor and is then tyrosine phosphorylated and activated to cleave phosphatidyl inositol 4,5 bisphosphate (PIP2) releasing diacylglycerol (DAG) and inositol tris phosphate (IP3) and activating protein kinase C (PKC) as shown in Figure Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009 by Academic Press. All rights reserved.

26 FIGURE 1.24 Dimerized hormone receptors (R) associate with the JAK family of cytosolic protein tyrosine kinases, and become phosphorylated on tyrosines. Proteins of the STAT family (S) of transcription factors that reside in the cytosol in the unstimulated state are recruited to the phosphorylated receptor. After phosphorylation by JAK, STATs dissociate from the receptor, form homodimers, and migrate to the nucleus where they activate gene transcription. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009 by Academic Press. All rights reserved.

27 Ρύθμιση της έκκρισης των ορμονών Μηχανισμός Αρνητικής Ανάδρασης Ορμόνη-Ορμόνη Υπόστρωμα- Ορμόνη Ηλεκτρολύτες- Ορμόνη Νευρικός Έλεγχος Χρονοτροπικός Έλεγχος Κύκλος ημέρας-νύχτας (κιρδάδιος ρυθμός) Κύκλος ύπνου εγρήγορσης Έμμηνος ρυθμός Εποχιακός ρυθμός Αναπτυξιακός ρυθμός

28 FIGURE 1.25 Components of a hormone response system. Responses produced by hormones generally are sensed by whatever apparatus activated the secretion and usually decrease further secretion. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009 by Academic Press. All rights reserved.

29 FIGURE 1.26 Negative feedback of hepatic glucose production by glucagon. ( ) = inhibits, (+) = stimulates. 29Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009

30 FIGURE 1.27 Negative feedback regulation of blood glucose concentration by insulin and glucagon. ( ) = inhibits, (+) = stimulates. 30

31 FIGURE 1.28 Positive feedback regulation of oxytocin secretion. (1) Uterine contractions at the onset of parturition apply mild stretch to the cervix. (2) In response to sensory input from the cervix (blue arrows), oxytocin is secreted from the posterior pituitary gland, and stimulates (green arrows) further contraction of the uterus, which, in turn stimulates secretion of more oxytocin (3) leading to further stretching of the cervix, and even more oxytocin secretion (4), until the fetus is expelled (5). 31

32 FIGURE 1.31 Changes in hormone concentrations in blood may follow different patterns. A. Daily rhythm in testosterone secretion. (From Bremer et al. (1983) J. Clin. Endocrinol. Metab. 56: 1278.) B. Hourly rhythm of LH secretion. (From Yamaji et al. (1972) Endocrinology 90: 771.) C. Episodic secretion of prolactin. (From Hwang et al. (1971) Proc. Natl. Acad. Sci. USA 68: 1902.) 32

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34 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

35 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

36 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

37 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ

38 FIGURE 2.8 Regulation of anterior pituitary hormone secretion. Environmental factors may increase or decrease pituitary activity by increasing or decreasing hypophysiotropic hormone secretion. Pituitary secretions increase the secretion of target gland hormones, which may inhibit further secretion by acting at either the hypothalamus or the pituitary. Pituitary hormones may also inhibit their own secretion by a short feedback loop. Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright 2009 by Academic Press. All rights reserved. 38

39 APXEΣ ΦYΣIOΛOΓIAΣ, TOMOΣ II ΠANEΠIΣTHMIAKEΣ EKΔOΣEIΣ KPHTHΣ