Evidence for pituitary regulation of somatic growth, insulin-like growth factors-I and -II, and their binding proteins in the fetal rat.
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)
Kim
J D
JD
Department of Neonatology and Pediatric Endocrinology, Stanford University School of Medicine, California 94305.
Näntö-Salonen
K
K
Szczepankiewicz
J R
JR
Rosenfeld
R G
RG
Glasscock
G F
GF
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004392:Dwarfism / Q000235:genetics / Q000503:physiopathology; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone