Hormone Metabolism

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  • 1.Hormone Metabolism BELLA MARILOU BAXA-DAGUPLO, MD Department of Biochemistry & Nutrition Fatima College of Medicine Our Lady of Fatima University (Review 09)

2. Hormones

  • from the Greek term ( ) "impetus
    • - to arouse to activity
  • substance synthesized in one tissue & transported
  • by circulatory system to act on another organ

Hormone Metabolism ON OFF Target cell Cell origin (Effects) 3. Hormone Metabolism

  • Endocrine
  • Paracrine
  • Autocrine

Functions of Hormones 4. Hormone and NeurotransmittersHormone Metabolism

  • Norepinephrine/Serotonin-> depression
  • oversensitivity to serotonin-> OCD behaviors
  • Dopamine-> Parkinsons disease
  • Too much dopamine in the limbic system and
  • not enough in the cortex-> personality given
  • to bouts of paranoia or (-) social interaction
  • norepinephrine(NE) ->aggression

5. Hormone and NeurotransmittersHormone Metabolism

  • Phenylethylamine + dopamine ->mild anti-
  • depressant effect
  • Phenylethylamine in the limbic system ->
  • feelings of bliss
  • oxytoxin->impulse to cuddle; multiple orgasm
  • norepinephrine w/ dopamine & phenylethylamine
  • -> give us the feeling of infatuation
  • too much stress in children can create permanently
  • levels of serotoninandlevels of NE ->creating
  • a potential of violent behavior

6. Hormone Metabolism General Characteristicsof Hormones

  • Not secreted at a uniform rate
  • Exert their effects in biocatalytic amounts
  • Turnover is varied and usually rapid
  • Exert multiple actions
  • Exhibit high degree of specificity
  • Different tissues may respond
    • differently to a given hormone

7. Regulation of Hormone Secretion A.Feedback Control 1) Negative Feedback 2) Positive Feedback Hormone Metabolism B.Neural Control - visual/ olfactory/ gustatory C.Chronotropic Control - sleep-wake cycle/ physiologic cycle 8. Regulation of Hormone Secretion Hormone Metabolism Feedback Control Negative Feedback

  • T3 and T4
  • inhibits secretion
  • of TRH and TSH

HPT Axis Hypothalamus TRH TSH T 3, T 4 + - + + - Anterior Pituitary Thyroid Increased metabolism 9. Regulation of Hormone Secretion Hormone Metabolism Feedback Control Positive Feedback

  • estrogen level
  • results to LH surge
  • during ovulation

Female HPG Axis + + Hypothalamus + Anterior Pituitary Ovaries Estrogen Progesterone + + + - - FSH LH GnRH 10. Forms of Hormone in the Circulation Hormone Metabolism A.Free Molecules (unbound) - water-soluble hormones B.Bound Molecules - water insoluble hormones - bound with specific globulins or transport proteins such as albumin, cortisol-binding globulin, and thyroid-binding globulin 11. Fates of Hormone Hormone Metabolism

  • A.Target cell uptake
  • B.Metabolic degradation
  • Urinary or biliary excretion
  • kidney and liver are the major sites of
  • hormone metabolism and degradation

12. Classification of Hormones I.According to Structure A. Protein hormones 1) Simple or polypeptide[insulin, glucagon,somatostatin, growth h., ACTH, MSH, PRL, CS ] 2) Complex or glycoprotein[TSH, FSH, LH, hCG] B. Steroid hormones[glucocorticoids,mineralocorticoids, sex androgens, retinoic a., calcitriol] C. Biogenic amine hormones[ thyroxine,catecholamines] II. According to Mechanism of Action A. Group 1 B. Group 2 Hormone Metabolism 13. Hormone Metabolism Classification of Hormones [Protein] A-Chain B-Chain Insulin and C-peptide Formation Ribosome ER Golgi A. Vesicles 14. Hormone Metabolism Classification of Hormones [Protein] Pro-opiomelanocortin Peptide Family 15. Hormone Metabolism Classification of Hormones [Steroids] 16. Classification of Hormones [Amines] Hormone Metabolism Some Biogenic Amines Dopamine CH 2-CH 2 NH 2HO HO CH -CH 2 NHCH 3 OH HO HO Epinephrine Tetraiodothyronine Norepinephrine CH -CH 2 NH 2 OH HO HO 17. Classification of Hormones Hormone Metabolism According to Mechanism of Action Group 1 Group 2 Type Steroids, thyroid h., Polypeptides and retinoic acid . catecholamines SolubilityLipophilic Hydrophilic Transport Protein Yes No Plasma T1/2 Longer Shorter Receptor IntracellularPlasma membrane Mediator HRC/HRE2nd messengers 18. Hormone Metabolism Steps Involved in Eliciting Response of Target Cell

  • Recognition and binding of the hormone
  • to specific receptor
  • 2)Coupling to generate signal
  • Changes in intracellular processes
  • brought about by the generated signal

19. Hormone Metabolism Receptors

  • specific proteins that must first bind a
  • hormone before cellular response can
  • be elicited
  • have at least 2 Functional domains:
  • 1) Recognition domain -binding domain
  • 2) Coupling domain -generates signal that
  • couples hormone recognition to some
  • intracellular function

20. Hormone Metabolism Classes: A.Cell surface receptors B.Intracellular receptors 1)Nuclear receptors 2)Cytoplasmic receptors Receptors 21. Cell Membrane Receptors Functional Domains: 1) Ligand-binding domain 2) Transmembrane domain 3) Cytoplasmic domainHormone Metabolism Receptors N C Typical cell membrane receptor (seven membrane-spanning domain) Extracellular Intracellular 22. Intracellular Receptors Functional Domains: 1) Ahormone bindingregion in the C-terminal 2) An adjacentDNA bindingregion 3) Aspecifier region(N-terminal) necessary for high-affinity binding to the proper region of DNA 4) One or more regions thatactivate or repress gene transcription Hormone Metabolism Receptors (1) (2) (3) N C 23. Hormone Metabolism Signal Transduction

  • process which occurs after a hormone
  • binds to a receptor
  • an intracellular signal is generated
  • [second messenger]which delivers
  • the hormonal message
  • amplifies the original signal converting
  • substrate molecules to products

24. Hormone Metabolism Signal Transduction Peptides Catecholamines Neurotransmitters Steroids Thyroid hormones Estrogen, RA Insulin, EGF,IGF-1 Growth hormone Prolactin Signal Transduction Pathways Enzyme Activation Nucleus 25. Hormone Metabolism Mechanism of Action[Group 1] Cytoplasm Nucleus Hormone Action with intracellular receptors + Activation + Specific Protein Transcription mRNA Translation mRNA Metabolic response Hormone response element (HRE) Hormone receptor complex (HRC) Receptor Steroid/Thyroid h. Thyroid h. 26. Hormone Metabolism Mechanism of Action[Group 1] Structural requirements for hormonal regulation ofgene transcription 5 3 Hormone response elements (HRE) Promoter element (PE) Gene Transcription Initiation site Termination Site 1 + Regulatory DNA region StructuralDNA region 27. Hormone Metabolism Mechanism of Action[Group 1] Hormones that bind to Intracellular receptors (Group 1)

  • Mineralocorticoids
  • Glucocorticoids
  • Androgens
  • Progestins
  • Estrogens
  • Calcitriol (1,25[OH] 2 -D 3 )
  • Retinoic acid
  • Thyroid hormones (T 3and T 4 )

28. Hormone Metabolism Mechanism of Action of Group 2 Hormones Effector Systems

  • Effector systems that produce cytosolic
  • second messengers (couple w/ G-protein)
  • for signal transduction
  • Adenylyl cyclase -cAMP
  • Guanylyl cyclase -cGMP
  • Phospholipase C - phosphoinositides
  • (DAG & IP 3 )
  • Calcium - calmodulin(Ca ++ )

29. Hormone Metabolism Mechanism of Action[Group 2] Effector Systems

  • Effector system as an intrinsic part of the
  • receptor

-does not require G-protein to transduce the physiologic action of the ligand -contains an enzymatic activity within the intracellular domain that phosphorylates tyrosine kinase residues 30. Mechanism of Action [Group 2] 31. Mechanism of Action [Coupling w/ G-protein] 32. Mechanism of Action [Coupling w/ G-protein] 33. Mechanism of Action [Coupling w/ G-protein] 34. Hormone Metabolism Mechanism of Action[Group 2] Adenylate cyclase cAMP ES Regulation through cAMP-dependent protein kinases Adenylate cyclase ATP Mg 2+ cAMP( ) 5-AMP Phosphodiesterase 4 cAMP C R R C Inactive protein kinase R R C Active protein kinase 2 + Protein Phosphoproteins PhosphatasePhysiologic effects 35. Hormone Metabolism Mechanism of Action[Group 2] Adenylate cyclase cAMP ES 1. Activators of adenylyl cyclase

  • Cholera toxin inactivates GTPase;
  • sis frozen in active form
  • Pertussis toxin prevents activation of
  • i subunit

2. Inhibitor of adenylyl cyclase

  • Phosphodiesterase hydrolyzes cAMP
  • to 5-AMP

36. Hormone Metabolism Mechanism of Action[Group 2] Hormone Action using cAMP Second Messeng