Growth hormone (GH) regulation of circulating insulin-like growth factor-I levels during sexual maturation of the GH-deficient dwarf (dw/dw) male rat.
In many mammalian species, circulating levels of insulin-like growth factor-I (IGF-I) rise during puberty. Previous studies manipulating testosterone levels in rats with normal GH secretion suggested that the pubertal IGF-I rise is regulated by an interaction between GH and sex steroids. Therefore, in a reciprocal study, IGF-I levels were examined during sexual maturation of the GH-deficient dwarf (dw/dw) rat which has a selective genetic deficiency of GH but normal sex steroid levels. Male dw/dw rats were treated with daily injections of recombinant human GH (200 micrograms/100 g body weight) or saline vehicle, from 28 to 70 days of age. Sexual maturation was determined to occur primarily between 42 and 63 days of age based on testis and seminal vesicle growth and plasma testosterone levels. GH treatment had no effect on seminal vesicle weights, plasma testosterone or gonadotrophins. GH administration resulted in a 7% increase in absolute testes weight (P < 0.05), but a 50% increase in body weight (P < 0.0001). These results supported previous findings that the reproductive development of dw/dw rats is essentially normal. Untreated dw/dw rats had no rise in IGF-I levels during sexual maturation. In contrast, treatment with GH produced a marked sustained rise in IGF-I levels (P < 0.0001). LIgand blots demonstrated GH induction of IGF-binding protein-3 (IGFBP-3) and an IGFBP cluster at 32 kDa. The initially high immunoreactive IGFBP-1 levels (> 600 ng/ml) decreased by 49 days of age after which untreated dw/dw rats had significantly higher IGFBP-1 levels than GH-treated dw/dw rats (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Crawford
B A
BA
Department of Obstetrics and Gynaecology, University of Sydney, New South Wales, Australia.
Dobbie
P
P
Bass
J J
JJ
Lewitt
M S
MS
Baxter
R C
RC
Handelsman
D J
DJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005640:Follicle Stimulating Hormone / Q000097:blood; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology*; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011869:Radioligand Assay; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012741:Sexual Maturation / Q000502:physiology*; D013002:Somatomedins / Q000032:analysis; D013737:Testis / Q000033:anatomy & histology
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013006:Growth Hormone