Evidence for pituitary regulation of somatic growth, insulin-like growth factors-I and -II, and their binding proteins in the fetal rat

Pediatr Res. 1993 Feb;33(2):144-51. doi: 10.1203/00006450-199302000-00012.


We investigated pituitary regulation of late-gestation fetal growth in the spontaneous dwarf rat, a strain with an autosomal recessive mutation (gene symbol dr) in the growth hormone (GH) gene resulting in complete isolated GH deficiency. GH-normal/GH-deficient (Dr/dr) females were crossed with Dr/dr or dr/dr males, producing both GH-deficient and GH-normal fetuses within the same litter. Pups were killed within 3 h after birth to approximate the developmental state of a late-gestation fetus. The body weight of GH-deficient fetuses was inhibited by 14% in comparison to GH-normal animals, but tail length remained unaffected. The brain and lungs were the only organs whose growth appeared to be pituitary-independent. Other organs showed moderate pituitary dependence in proportion to body weight. Serum IGF-I and IGF-II were reduced by 73% and 52%, respectively, in the absence of GH. The major IGF-binding proteins (IGFBP) were analyzed by Western ligand blot. The predominant 26- to 30-kD IGFBP band normally seen in neonatal rat serum was greatly increased in GH-deficient sera, to 250% of GH-normal sera as measured by densitometry. However, addition of alpha-Hec 1 antibody to IGFBP-2, which has been used to identify IGFBP-2 as the major neonatal IGFBP, resulted in immunoprecipitation of only a small amount of the 26- to 30-kD band from the GH-deficient fetuses, suggesting the presence of an additional IGFBP. Northern analysis of GH-deficient livers did not reveal any visible increase in IGFBP-1, IGFBP-2, or IGFBP-4 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Dwarfism / genetics
  • Dwarfism / physiopathology
  • Embryonic and Fetal Development / physiology
  • Female
  • Fetal Blood / metabolism
  • Fetus / physiology*
  • Growth Hormone / deficiency*
  • Growth Hormone / genetics
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • Pituitary Gland / physiology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Mutant Strains


  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Growth Hormone