title: Effect of testosterone on insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the hypophysectomized rat.
abstract: Circulating levels of insulin-like growth factor-I (IGF-I) increase during puberty, concurrent with an increase in the levels of GH and the gonadal steroids. The relationship between the changes observed in IGF-I and testosterone (T) levels are not understood. This study was designed to determine whether T has a direct effect on IGF-I serum levels, liver IGF-I gene expression, and epiphyseal growth plate IGF-I and IGF-I receptor gene expression. Hypophysectomized castrated rats were divided into four groups of six animals. The T group was treated with sc T for 5 days. The GH group was treated with a single dose of GH. The GH plus T group was treated with T for 5 days and with GH on the last day of treatment. The control group was injected for 5 days with vehicle alone. Serum IGF-I levels in the T group were not significantly different from those in the control group, and the levels in the GH plus T group were not significantly different from those in the GH group. There was an 11-fold increase in liver IGF-I mRNA abundance in the GH group compared to the control group (P less than 0.01). Liver IGF-I mRNA levels in the T group were not significantly different from those in the control group. When liver IGF-I mRNA levels in the GH plus T group were compared to those in the GH-treated group, no significant differences were found. In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups. IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group. IGF-I receptor mRNA abundance was not significantly different in the T group compared to that in the control group. GH decreased IGF-I receptor mRNA by 2.3-fold, but T treatment before GH injection did not change this effect. We conclude that in castrated hypophysectomized rats, T does not stimulate IGF-I gene expression in the liver, nor does it increase IGF-I serum levels. T alone also does not have a stimulatory effect on IGF-I or IGF-I receptor gene expression in the epiphyseal growth plate region.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Division of Pediatric Endocrinology, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: M
authors.initials: M
authors.lastname: Phillip
authors.forename: T
authors.initials: T
authors.lastname: Palese
authors.forename: E R
authors.initials: ER
authors.lastname: Hernandez
authors.forename: C T
authors.initials: CT
authors.lastname: Roberts
authors.forename: D
authors.initials: D
authors.lastname: LeRoith
authors.forename: A A
authors.initials: AA
authors.lastname: Kowarski
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D015870:Gene Expression / Q000187:drug effects; D013006:Growth Hormone / Q000494:pharmacology; D006132:Growth Plate / Q000187:drug effects / Q000502:physiology; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin; D012016:Reference Values; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D016375:Antisense Elements (Genetics); D015347:RNA Probes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone