Cell to Cell Communication

Transcription

1 Review #1 15 Review using OPAL figures Review using class web PDF Preview of test #1 Cell to Cell Communication 1

2 Communication Strategies endocrine neurocrine paracrine autocrine Endocrine System Overview 2

3 Pituitary Gland Hypothalamus 3

4 Releasing Hormones TRH GnRH CRH GHRH Peptide Hormones (POMC) ßLPH ACTH ßEND γlph ACTH ßENK ßMSH CLIP αmsh γmsh 4

5 Steroid Hormones cyclopentane - perhydrophenantrene group cholesterol Steroid Pathways 5

6 (from wikipedia) Mito SER Nuclear Receptors Structure 6

7 Control of Transcription Receptors (G linked and TK) 7

8 G Protein Coupled Receptor G - Protein 8

9 GPCR and Channel GPCR and Enzyme 9

10 DAG and PLC Arachedonic Acid 10

11 Receptor containing Kinase Parathyroids 11

12 Thyroid s Clear (C) Cells stimulates Thyroid Gland 12

13 Thyroid Hormone Synthesis Thyroid Hormone Synthesis 13

14 Thyroid Hormone Effects Muscle, increase glucose uptake CNS, development and maturation (promotes neuronal branching and myelinization of nerves) CV, increases CO and the number of red blood cells Liver, promotes IGF production and glycogen formation Bone, promotes bone growth Thyroid Hormone Effects The elements required for thyroid hormone action are well recognized, but the interaction among the various pathways has been challenging to understand. Thyroid hormone interacts with a wide variety of signaling pathways, and its action is modulated based on nutritional and iodine status. A range of conditions with disordered thyroid signaling has allowed us to identify key regulatory pathways that are potential therapeutic targets. The availability of TR isoform selective agonists and the recent reports of patients with RTH due to TRα mutations, as well as those homozygous for TRβ mutations, are strong evidence for TR isoform specificity. The role of the pituitary in responding to a defect in a thyroid hormone action pathway is central to the resulting phenotype. These pathways, as well as the role of thyroid hormone in metabolism, cardiac function, and oncogenesis, are likely to be the focus in applying these findings. Brent GA, Mechanism of thyroid hormone action. J Clin Invest. 2012;122(9): doi: /jci

15 Thyroid Hormone Effects Nuclear action of thyroid hormone. Shown are the key components required for thyroid hormone action, as demonstrated by a range of clinical observations. (A) The TR gene has 2 major isoforms, TRβ and TRα; the structures of TRα1 and TRα2 (non T3-binding) and TRβ1 and TRβ2 are shown. Brent GA, Mechanism of thyroid hormone action. J Clin Invest. 2012;122(9): doi: /jci Thyroid Hormone Effects (B) The major thyroid hormone forms, T4, T3, and rt3. Brent GA, Mechanism of thyroid hormone action. J Clin Invest. 2012;122(9): doi: /jci

16 Thyroid Hormone Effects (C) Circulating T4 is converted locally in some tissues by membranebound D2 to the active form, T3. D3 converts T3 to the inactive rt3. Brent GA, Mechanism of thyroid hormone action. J Clin Invest. 2012;122(9): doi: /jci Thyroid Hormone Effects (D) In specific tissues, such as brain, transporters such as MCT8 transport T4 and T3 into the cell. Unliganded TR heterodimerizes with RXR and binds to a TRE and then to a corepressor, such as NCoR or SMRT, repressing gene expression. T3 binding to the ligand-binding domain results in movement of the carboxy-terminal helix 12, disruption of corepressor binding, and promotion of coactivator binding, which then leads to recruitment of polymerase III and initiation of gene transcription. Brent GA, Mechanism of thyroid hormone action. J Clin Invest. 2012;122(9): doi: /jci

17 Endocrine Overview Review #1 15 Review using OPAL figures Review using class web PDF Preview of test #1 17

18 Basic Concepts & Methods Some general concepts for the course a) definition of hormone and of endocrine, neurocrine, paracrine transmission b) methodologies used in endocrinology (RIAs, RRA, ICC, hybridization, ) c) how liposoluble and watersoluble hormones are made in general (SER vs RER) d) hormone story line as a trick to think of steps involved in hormone function Roughly there are 2-3 test questions per punch-line The Story Line Table Things to look up in the table a) hormones that are water soluble and those that are lipo soluble b) hormones involved in hierarchies (gonadal, adrenal, thyroid, ) c) hormones involved in metabolism (glucose, calcium, sodium, water, ) d) inputs to endocrine glands and hormone effects on different organs Roughly there are 2-3 test questions per punch-line 18

19 The Negative Feedback Reflex-arc like-models and the - Fb for different hormones a) inputs, integrators, -Fb in the control of different hormones (the refrigerator and the circle ) b) role of the hypothalamus in neuroendocrine control of the endocrine system c) theoretical components of a control system, homeostasis and rheostasis d) endocrine and neuroendocrine control and their disruption in pathology Roughly there are 2-3 test questions per punch-line Lipo-soluble Hormones Some basic points on mechanism of action of lipo-soluble hormones a) intracellular receptors mainly but also membrane receptors (experiments) b) effect on protein synthesis mainly, but some also have membrane receptors c) cys and trans elements involved in regulation at the promoter level.. integrator d) permissive effects of some liposoluble hormones (e.g. T3-4, Cortisol, E2, ) Roughly there are 2-3 test questions per punch-line 19

20 Water-soluble Hormones Some basic points on mechanism of action of water soluble hormones a) plasma membrane receptors but they also have access to the genome b) an ultimate effect on channels and enzymes underlies endocrine action c) GPCR and Tyr-kinase links, different paths to protein phosphorylation d) Permissive effects of some watersoluble hormones (e.g. Prl on LH receptors) Roughly there are 2-3 test questions per punch-line Hypothalamic-Pituitary Unit Some basic points on the hypothalamic pituitary connection a) hypothalamic anterior pituitary portal system (neurohormones, amplification) b) hypothalamic posterior pituitary system (a good example of neuronal events) c) the pituitary receives 2/3 of the outputs from PVN (a main brain integrator) d) the median eminence as a final brain integrator site for endocrine function Roughly there are 2-3 test questions per punch-line 20

21 Anterior Pituitary Hormones Some basic points on anterior pituitary (AP) hormones a) most AP hormones are tropic / trophic hormones that act on other endocrine glands b) all AP hormones are controlled by hypothalamic hypophysiotropic neurohormones c) the hypothalamic AP unit acts as an integrator and amplification control unit d) the hypothalamic AP link is a vascular one since both tissues have different origin Roughly there are 2-3 test questions per punch-line Posterior Pituitary Hormones Some basic points on posterior pituitary (PP) hormones a) PP hormones are neurohormones made in the hypothalamus and released in the PP b) the hypothalamus and PP have the same embryological origin (as opposed to AP) c) PP hormones are involved in water metabolism and myoepithelial contraction d) AVP is also released in ME and acts in AP as a CRH, albeit by different mechanism Roughly there are 2-3 test questions per punch-line 21

22 AVP, OT and Melatonin AVP, OT, and melatonin a) AP hormones (ACTH, GH, PRL, TSH, LH, FSH, MSH, ßEND) see below (*) b) PP hormones (AVP, OT) see below (*) c) Pineal hormone (Melatonin) see below (*) (*) Expand story line for each of these hormones following an order such as: origin, stimuli, biosynthesis, release, target, action mechanism, effect, integration, others Roughly there are 2-3 test questions per punch-line Ca - Regulating Hormones Ca regulating hormones, PTH, vitd, calcitonin a) PTH b) vitd c) Calcitonin (*) Expand story line for each of these hormones following an order such as: origin, stimuli, biosynthesis, release, target, action mechanism, effect, integration, others Roughly there are 2-3 test questions per punch-line 22

23 Thyroid - Related Hormones Thyroid regulating hormones, T3-T4, TSH, TRH a) T3-T4 b) TSH c) TRH (*) Expand story line for each of these hormones following an order such as: origin, stimuli, biosynthesis, release, target, action mechanism, effect, integration, others Roughly there are 2-3 test questions per punch-line Review #1 15 Review using OPAL figures Review using class web PDF Preview of test #1 23

24 For the test next Wednesday 1 Be outside the lecture room by 12:15 PM 2 as I call you, walk to the stage of the room and 3 leave your carry on in front of the lecture hall 4 pick-up your test & scantron from the instructor 5 please, sit exactly where the instructor tells you 6 fill name, seat, and web-id# in test AND scantron 7 a web-id # is any 5 digit personal number Test #1 Endocrinology, test#1, JP Advis Name Student ID Web ID Seat Note: all the above info also goes in the scantron, with the webid and the seat in the upper right corner. FOR ALL QUESTIONS SELECT THE BEST ANSWER FROM THE OPTIONS GIVEN 24

25 SCANTRON SHEET Write name and bubble it scantron s upper right corner Write webid and seat # Write RU-ID# and bubble it Write web-id# and bubble it Bubble your answers DO NOT bubble your birthday. No gifts will be send to you Endocrine Physiology story line I suggest you put this information into a table YOU design 25