Class Notes (836,246)
Canada (509,715)
Physiology (903)
PHGY 210 (301)

Endocrinology 1.pdf

11 Pages
Unlock Document

PHGY 210
Anne- Marie Lauzon

WEEK  1   Wednesday,  January   5 ,  2011   PHGY  210   Dr.  White     Course  Information   • Endocrinology  USCAs   o Daniel  Marinescu  ([email protected] )   o Kelita  Singh  ([email protected] )   • (30%)  Midterm  Exam:  Wednesday,  March  2,  2011   from  6:30  p.m.  –  8:00  p.m.     o Material:  Endocrinology,  Respiration  &  Cardiovascular  -­‐>  material  covered  up  to  February  18   lectures.     • (70%)  Final  Exam:  During  final  exam  period  in  April.     Endocrinology   • Endocrinology  is  necessary  for   coordination  of  physiological  processes  that   take  place  simultaneously  in  the  living  organism   o Examples:  movement,  respiration,  circulation,  digestion,  excreti on,  and   metabolism   • The  CNS  and  the  endocrine  system  represent  the  two  major  means  by  which   these  functions  are  coordinated   • Long  distance  communication     o Communication  between  cells  that  are  not  in  contact  is  achieved  through   the  secretion  of  a  number  of  chemical  substances  by  releasing  cells.  These  substances  then  interact   with  specific  receptors  on  distant  target  cells     o Signaling  through  these  receptors  ultimately  leads  to  a  physiological  effect     Endocrine  Signaling   • Involves  hormone  secretion  into  the  blood  by  an  endocrine  gland   • The  hormone  is  then  transported  by  the  blood  to  a  distant  target  site   • Example:  anterior  pituitary  gland  will  release  a  hormone  (LH/FSH)  into  the   blood  that  will  travel  to  the  gonads  and  react  with  specific  rec eptors  leading  to   a  physiological  response  in  the  gonads.     Neuroendocrine  signaling     • This  is  fundamentally  the  same  as  endocrine  signaling  except  that   the  cell  that   is  the  source  of  the  hormone  is  neuronal  in  nature   • Ex:  upstream  of  the  anterior  pituitary,   we  have  the  hypothalamus  (neuronal).   This  can  release  hormone  A  that  will  interact  with  the  anterior  pituitary  leading  to  another  hormonal   response  B  on  the  level  of  the  pituitary.     Paracrine  and  Autocrine  Signaling   • Not  all  signaling  is  long -­‐distance   • Paracrine  and  Autocrine  signaling  deal  with   close-­‐ proximity  signals  WITHOUT  entering  the  bloodstream   o Ex:  cells  in  the  intestinal  lumen  can  release   substances  that  cause  a  physiological   difference  in  the  adjacent  cells  of  the  lumen     • Can  be  cells  of  the  same   cell  type  or  other  cell  type     • Regardless  of  cell  types,   signaling  between  adjacent  cells  is  called  PARACRINE  SIGNALLING   • Signaling  from  a  cell  back  onto  itself  is  called  AUTOCRINE  SIGNALLING     1   WEEK  1   o A  cell  is  induced  to  release  a  substance  (ex:  growth  factor)  yet  i t  also  produces  and  expressed  the   receptor  for  that  hormone.  So  the  secreted  substance  is  specifically  binding  the  receptor  and   leading  to  self-­‐signaling.     Communication  by  Hormones  ( Six  Steps)   • Each  of  the  following  are  potential  sites  of  regulation   1. Synthesis  of  the  hormone  by  endocrine  cells  (or  neurons  in  the  case  of   neurohormones/neuroendocrinology)   a. Can  be  regulated  by  upstream  physiological  signals   b. Ex:  hormone  A  can  react  with  the  receptor  of  a  cell  leading  to  synthesis  of  hormone  B  by  that  cell   2. Release  of  the  hormone  by  the  endocrine  cells  (or  neurohormones  by  neurons)   a. Release  is  not  controlled  for  some  hormones .     b. For  many  hormones,  release  can  be  critical  (ex:  female  reproductive  endocrinology)   3. Transport  of  the  hormone  or  neurohormone  to  the  targ et  site  by  the  blood  stream   a. Most  of  the  time,  there  are  binding  proteins  (albumin  or  specific  bindin   proteins) b. Ex:  glucocorticoids  bind  to  cortico  binding  proteins  and  Vit  D  VDP  (vit  d  binding  protein)   c. Can  have  effects  on  signaling  but  will  not  be  covered   4. **  Detection  of  the  hormone/neurohormone  by  a   specific  receptor  protein  ON  THE  TARGET  CELLS   a. Receptors  are  ON  the  cells  because  the  vast  majority  of  hormones   cannot  penetrate  the  cell   b. There  are  still  a  subset  of  steroid  hormones  and  vitamin  D  that  are  lipid  soluble  and  resemble   membrane  components  and  thus  can  still  travel  across  the  plasma  membrane     5. **  Change  in  cellular  metabolism  triggered  by  the  hormone-­‐receptor  interactions   a. This  binding  event  elicits  a  specific  biochemical  response  in  the  cell   6. Removal  of  the  hormone  –  often  terminating  the  cellular  response   a. Physical/metabolic  removal  of  hormone  causing  it’s  inactivation     “Classical”  Endocrine  Organs   • Brain     o Particularly  hypothalamus,  anterior  and  posterior  pituitary   • Thyroid  Glands   • Parathyroid  Glands   o Parathyroid  physiology  is  NOT  THE  SAME  as  thyroid.  Just  named  this  way   because  they  are  physically  stuck  to  the  thyroid.   • Adrenal  Glands   o Composed  of  anatomically  distinct  layers  above  the  kidneys   o Important  hormone-­‐producing  cells   o Produce  glucocorticoids,  corticosteroids,  mineralocorticoids ,  some  sex   steroids,  etc.   o Detect  signals  coming  from  the  hypothalamus /pituitary   • Pancreas   o Produces  insulin   • Ovaries  (female)  Testes/Gonads   (male)   • Heart   o Neo-­‐classical  endocrine  organ   o Produces  atrial  natriuretic  peptides   (ANP)  –  controlling  blood  pressure     Hypothalamic-­‐Pituitary  (HP)  Signaling   • HP  X-­‐Axis  refers  to:  Hypothalamus  signaling  to  the  pituitary  that  then  signals  to  some   end-­‐organ   • HP  A-­‐Axis  refers  to  the  hypothalamus-­‐pituitary-­‐adrenal  pathway   • The  hypothalamus  and  pituitary  are  adjacent  to  each  other,  but  anatomically  and   histologically  different   o Hypothalamus  is  neuronal  the  pituitary  contains  specialized  non-­‐neuronal  endocrine  cells.     2   WEEK  1   o They  are  connected  by  the  Hypothalamic-­‐Hypophyseal  Portal  System   § From  the  hypothalamus  to  the   adenohypophysis  (anterior  pituitary)   • Hypothalamic  neurohormones  either  activate  or  inhibit   activity  of  one  of  the  six  types  of  hormone  producing  cells  in   the  anterior  pituitary   • If  produced  by  the  hypothalamus  and   stimulates  release  of   hormones  =  RELEASING  FACTOR.  If  the  substance   inhibits   release  of  hormones  =  INHIBITING  FACTOR     Classes  of  Hormones  Based  on  Their  Structure     • Hormones  have  many  different  structur es   • You  cannot  simply  look  at  a  structure  and  classify  it  as  a   hormone   • Many  hormones  are  proteins   o Glycoproteins  or  polypeptides   • Structure  of  hormone  DOESN’T  give  information  about  the   type  of  receptor  it  interacts  with   • There  are  also  non-­‐proteinaceous  hormones  such  as  steroids   o Aldosterone,  Estradiol,  Testosterone,  Progesterone,  Vitamin  D  (steroid  derivative),  Cortisol   • Structure  of  hormone  DOESN’T  tell  you  about  the  physiology  of  the  hormone  as  well   o Estradiol  and  testosterone  have  obviously  different  physiolo gical  consequences   • Missing  from  this  list  is   ionic  calcium  that  interacts  with  calcium  sensor  receptor   o This  will  detect  levels  of  calcium  based  on  the  amount  of  calcium  ions  that  are  bound  to  the   receptor  and  will  lead  to  signal  generation   o Calcium  will  act  like  a  hormonal  substance  in  this  case   • Glycoproteins  and  polypeptides  ARE  CODED  BY  GENES   o There  are  genes  for  Luteinizing  Hormone  (LH),  Insulin,  Glucagon,  etc.   o There  ARE  NOT  genes  for  Aldosterone,  Testosterone,  etc.   § Instead,  there  are  genes  for  enzymes  necessary  the  biosynthesis  of  amines/steroids     Synthesis  of  Protein  Hormones   • The  gene  for  insulin  will  have  a  coding  region  for  the  polypeptide,  but  will  also  have  an  additional   N-­‐ terminal  sequence  called  the  pre-­‐pro  region  of  insulin   • Any  polypeptide  desti ned  for  secretion  is  produced  with  a  pre -­‐pro  polypeptide     o This  serves  to  direct  the  protein  to  the  secretory  apparatus   o Without  the  pre -­‐pro  sequence,  the  protein  would  never  leave  the  cytoplasm.     • Mechanism:   o The  sequence  causes  the  mRNA  to  be  translated  on  t he  RER  where  it  is  then  transferred  to  the  golgi   apparatus.  It  is  packaged  into  secretory  vesicles.   o During  this  process,  the  pre -­‐pro  sequence  is  cleaved  off   o Sugar  moieties  can  also  be  added  during  processing   o By  the  time  it  is  secreted  from  a  vesicle,  the   hormone  is  in  it’s  mature  form     Steroid  Hormone  Structure     • They  all  share  a  common  4-­‐ring  structure  –  the  steroid  backbone   • The  best-­‐known  steroid  is  cholesterol,  which  can  lead  to  the  metabolic   generation  of  cortisol,  aldosterone,  testosterone,  and  estrad iol.  Cholesterol   differs  from  them  because  it  has  a  long  side -­‐chain.   • Cortisol  is  a  glucocorticoid,  while  aldosterone  is  a  mineralocorticoid.  They   have  related  structures  and  thus  can  undergo  cross -­‐talk  between  these  two     3   WEEK  1   steroids  and  their  receptors  under  c ertain  conditions.  (ex.  Cortisol  can  interact  with  aldosterone  receptor   and  vice-­‐versa)   • Testosterone  has  a  methyl  group  and,  when  removed,  testosterone  spontaneously  aromatize s  to  get   estradiol   o The  different  affinity  of  the  two  steroids  is  explained  by  the  benzene  ring.  When  aromatized  it  is  flat   and  when  non-­‐aromatized  the  ring  is  kinked.   o Aromatase  can  convert  testosterone  to  estradiol   • Males  produce  their  own  estrogen  for   local  use  by  certain  cell  types     Structures  of  Thyroid  Hormones   • Iodine  is  attached  to  the  structure  of  Thyroid  hormones   • Table  salt  has  some  sodium  iodide  in  it  to  prevent  thyroid  hormone   deficiency  known  as  cretinism     • There  are  two  forms  of  thyroid  hormone   T4  and  T3  –  they  both  bind  the   same  thyroid  receptor     Mechanism  of  Hormone -­‐Receptor  Interaction  -­‐-­‐  “Lock  and  Key”   • A  hormone  recognizes  one  particular  membrane  receptor  over  another  because  of  the  complementary   chemical  structure   • Ex:  the  androgen  receptor  will  not  bind  to  estrogen  with  high  affinity  due  to  the  altered  3 -­‐dimensional   structure  of  the  ring   • The  lock  and  key  interaction  leads  to  a   conformational  change  of  the  receptor  and  leads  to  a   downstream  signaling  event  inside  the  cell  (ex:  by  a  regulatory  protein)   Properties  of  Hormone  Receptors   1. SPECIFICITY:  recognition  of  a  single  horm one  or  hormone  family   2. AFFINITY:  high  affinity  for  the  hormone   –  ie:  binds  hormone  at  its  physiological  concentration   a. Do  not  want  receptor  binding  at  excessive  or  deprived  levels  for  proper  regulation   3. SATURABILITY:  should  show  saturability   –  ie:  a  finite  number  of  receptors   4. MEASURABLE  BIOLOGICAL  EFFECT:  a  measurable  biological  response  due  to  interaction  of  a  hormone   with  its  receptor     Receptor  Regulation   • Receptors  can  be  UPregulated  by  INCREASING  THEIR  ACTIVITY   or  by  INCREASING  SYNTHESIS  in   response  to  hormone   o Ex:  type  II  diabetes  you  have  an  abundance  of  insulin,  but  no  signaling.  This  is  because  of  a  negative   feedback  loop  of  the  receptor  or  downregulation  of  receptor  expression.   • Receptors  can  be  DOWNregulated  by  DECREASING  THEIR  ACTIVITY   or  by  DECREASING  SYNTHESIS   in   response  to  hormone.     3  Mechanisms  a  Hormone  Can  Use  to  Exert  Effects  on  Target  Cells   1. Direct  effects  on  function  at  the  cell  membrane   a. Ex:  Interaction  at  the  membrane  affects  transport  at  the  membrane  directly   • We  can  also  have  more   long-­‐term  effects  that  require  signaling  mechanisms  to  get  to  the  nucleus  and  affect   transcription   2. Intracellular  effects  mediated  by  second  messenger  systems   a. Ex:  G-­‐protein  coupled  hormone  receptors   i. This  leads  to  production  of  cAMP  and  eventually  a  biologic al  effect   ii. Will  alter  gene  transcription  eventually,  but  does  it  through  a  series  of  e  s 3. Intracellular  effects  mediated  by  genomic  or  nuclear  action   a. These  are  steroid  receptors  typically   i. In  unbound  form  they  are  found  in  the  cytoplasm   ii. When  bound,  they  tr anslocate  to  the  nucleus  where  they  bind   specific  sequences  and   subsequences  of  DNA     4   WEEK  1   b. They  alter  the  rates  of  transcription  of  these  genes   c. In  some  cases,  the  unbound  receptor  will  be  found  in  the  nucleus  already  and  the  steroid  will  be  in   the  nuclear  membrane  before  binding  it.       i. This  is  the  case  for  thyroid  hormone.                             5   WEEK  1   Friday,  January  7 ,  2010   PHGY  210   Dr.  White     Feedback  Control  of  Hormone  Secretion   • Hormone  secretion  is  precisely  regulated  by  feedback  mechanisms   o Ex:  an  excess  of  hormone/hormonal  activity  leads  to  a  diminution  of   hormone  secretion   o Similarly,  a  deficiency  of  hormone  leads  to  an  increase  in  hormone   secretion   • Calcium  (Ca )  acts  in  a  negative  feedback  loop  to  regulate  plasma  calcium   levels   o Calcium  binding  to  the  recep tor  modulates  activity  of  the  receptor.   The  total  amount  of  calcium  binding  (dependent  on  blood  calcium   levels)  determines  the  regulation.   2+ • Under  low  plasma  Ca ,  we  have  stimulation  of  parathyroid  glands  that   leads  to  synthesis  and  release  of  parathyroid   hormone  (PTH).  This  acts  on  bone,  kidney  and  gut  to   increase  bone  resorption  to  increase  plasma  calcium.     • Now,  calcium  will  be  binding  to  the  receptor   at  normal  levels  and  will  tone   down  the  stimulation  of  parathyroid  glands  as  a  negative  feedback   mechanism.     Hormonal  Feedback  Mechanisms   • Can  also  have  a  double  negative-­‐feedback  loop  that  goes  not  only  to  the   anterior  pituitary,  but  also  to  the  hypothalamus.  This  shuts  down  signaling   through  the  HP-­‐Axis  (hypothalamic-­‐pituitary)   • Stress/other  brain  inputs   stimulate  the  hypothalamus,  this  leads  to  an   increase  in  CRH  secretion  (Corticotropin  releasing  hormone)   • The  increase  in  Plasma  CRH  levels  (H3)   causes  the  anterior  pituitary  to   increase  ACTH  secretion  (adrenocorticotropic  hormone)   • This  increases  plasma  ACT H  (H2)   • The  adrenal  cortex  will  increase  cortisol  (glucocorticoid)  secretion   leading  to  an  increase  in  plasma   cortisol  (H1)   • Cortisol  will  act  on  target  cells,  but  will  also  play  a  role  in  negative  feedback   o Cortisol  will  tone  down  ACTH  secretion  by  the  ante rior  pituitary  and  will  decrease  CRH   secretion  by  the  hypothalamus     • Such  feedback  mechanisms  are   self-­‐limiting     Endocrine  Glands  and  Their  Secretions   1. Anatomic  location   2. Hormones  secreted   3. Chemical  nature  of  hormones   4. Effects   5. Mechanism  of  action   6. Control  of  release   7. Problems   a. Deficiency  or  Excess   8. Treatment     Pituitary  Gland   • Anatomy:  Two  distinctly  differe
More Less

Related notes for PHGY 210

Log In


Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.