RT Book, Section
A1 Cogan, Joy D.
A1 Phillips, John A.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181453850
T1 Inherited Defects in Growth Hormone Synthesis and Action
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181453850
RD 2024/04/24
AB Human  growth  hormone  (hGH,  or  somatotropin)  is  essential  for  normal  postnatal  growth.  It  is  a  191-amino  acid  protein  that  is  released  from  the  anterior  pituitary  gland  on  stimulation  by  growth  hormone-releasing  hormone  (GHRH,  or  somatocrinin),  a  factor  produced  by  the  hypothalamic  region  of  the  brain.  Like  other  pituitary  hormones,  hGH  acts  on  target  tissues,  in  this  case  primarily  the  liver,  to  cause  synthesis  and  release  of  a  second  hormone  mediator,  insulin-like  growth  factor  (IGF)  I,  also  called  somatomedin  C,  into  the  systemic  circulation.  IGF-I  is  a  growth-accelerating  peptide  that  acts  directly  on  cartilage  to  promote  bone  growth.Deficiency  of  human  growth  hormone  (hGH)  production  causes  metabolic  alterations  and  growth  failure.  While  most  cases  of  hGH  deficiency  are  idiopathic,  17  known  single  gene  disorders  as  well  as  a  variety  of  other  genetic  disorders  and  syndromes  are  associated  with  deficiency  of  hGH  or  defective  action.  These  genetic  disorders  are  caused  by  alterations  in  the  hGH  gene,  alterations  of  distant  loci  (such  as  Pit-1,  Prop-1,  or  GHRHR)  that  cause  hGH  deficiency  through  epistatic  effects,  or  alterations  of  genes  (such  as  the  growth  hormone  receptor  gene  (GHR))  that  affect  the  response  to  hGH.Deficiency  of  hGH  was  treated  in  the  past  by  replacement  with  exogenous  hGH  isolated  from  cadaver  pituitaries.  Because  of  the  accompanying  danger  of  transmission  of  infectious  neurodegenerative  disease  (Creutzfeldt-Jakob  disease;  MIM  123400),  alternative  methods  of  treatment  are  now  used.  These  include  replacement  with  biosynthetic  hGH  or,  in  some  cases,  treatment  with  GHRH.  The  potential  for  hGH  gene  therapy  has  been  demonstrated  in  animals.Human  chorionic  somatomammotropin  (hCS,  or  human  placental  lactogen)  has  similar  biologic  activities,  but  it  is  much  less  potent  than  hGH.  During  pregnancy,  maternal  hCS  levels  are  very  high  and  approximately  300  times  greater  than  fetal  levels.  While  human  chorionic  somatomammotropin  (hCS)  is  thought  to  be  important  in  maternal  carbohydrate  and  fat  metabolism,  normal  fetal  growth  occurs  in  pregnancies  in  which  it  is  absent.Two  genetic  disorders  of  the  hCS  loci  have  been  described.  While  these  alterations  lead  to  deficiency  or  absent  hCS  production,  affected  individuals  are  thought  to  be  asymptomatic.