IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice.
Autor/es:
MARIA CECILIA RAMIREZ; GUILLERMINA MARIA LUQUE; ANA MARIA ORNSTEIN; DAMASIA BECU-VILLALOBOS
Revista:
JOURNAL OF ENDOCRINOLOGY
Editorial:
BIOSCIENTIFICA LTD
Referencias:
Año: 2010 vol. 207 p. 301 - 308
ISSN:
0022-0795
Resumen:
Abnormal exposure to steroid hormones within a critical
developmental period elicits permanent alterations in female
reproductive physiology in rodents, but the impact on the
female GH axis and the underlying sexual differences in
hepatic enzymes have not been described in detail. We have
investigated the effect of neonatal androgenization of female
mice (achieved by s.c. injection of 100 mg testosterone
propionate (TP) on the day of birth: TP females) on the
GHRHsomatostatinGH axis and downstream GH targets,
which included female and male predominant liver enzymes
and secreted proteins. At 4 months of age, an organizational
effect of neonatal testosterone was evidenced on hypothalamicmg testosterone
propionate (TP) on the day of birth: TP females) on the
GHRHsomatostatinGH axis and downstream GH targets,
which included female and male predominant liver enzymes
and secreted proteins. At 4 months of age, an organizational
effect of neonatal testosterone was evidenced on hypothalamic
Ghrh mRNA level but not on somatostatin (stt)
mRNA level. Ghrh mRNA levels were higher in males than
in females, but not in TP females. Increased expression in TP
females correlated with increased pituitary GH content and
somatotrope population, increased serum and liver IGF-I
concentration, and ultimately higher body weight. Murine
urinary proteins (MUPs) that were excreted at higher levels in
male urine, and whose expression requires pulsatile occupancy
of liver GH receptors, were not modified in TP females
and neither was liver Mup 1/2/6/8 mRNA expression.
Furthermore, a male predominant liver gene (Cyp2d9) was
not masculinized in TP females either, whereas two female
predominant genes (Cyp2b9 and Cyp2a4) were defeminized.
These data support the hypothesis that neonatal steroid
exposure contributes to the remodeling of the GH axis and
defeminization of hepatic steroid-metabolizing enzymes,
which may compromise liver physiology.mRNA level but not on somatostatin (stt)
mRNA level. Ghrh mRNA levels were higher in males than
in females, but not in TP females. Increased expression in TP
females correlated with increased pituitary GH content and
somatotrope population, increased serum and liver IGF-I
concentration, and ultimately higher body weight. Murine
urinary proteins (MUPs) that were excreted at higher levels in
male urine, and whose expression requires pulsatile occupancy
of liver GH receptors, were not modified in TP females
and neither was liver Mup 1/2/6/8 mRNA expression.
Furthermore, a male predominant liver gene (Cyp2d9) was
not masculinized in TP females either, whereas two female
predominant genes (Cyp2b9 and Cyp2a4) were defeminized.
These data support the hypothesis that neonatal steroid
exposure contributes to the remodeling of the GH axis and
defeminization of hepatic steroid-metabolizing enzymes,
which may compromise liver physiology.Ghrh mRNA levels were higher in males than
in females, but not in TP females. Increased expression in TP
females correlated with increased pituitary GH content and
somatotrope population, increased serum and liver IGF-I
concentration, and ultimately higher body weight. Murine
urinary proteins (MUPs) that were excreted at higher levels in
male urine, and whose expression requires pulsatile occupancy
of liver GH receptors, were not modified in TP females
and neither was liver Mup 1/2/6/8 mRNA expression.
Furthermore, a male predominant liver gene (Cyp2d9) was
not masculinized in TP females either, whereas two female
predominant genes (Cyp2b9 and Cyp2a4) were defeminized.
These data support the hypothesis that neonatal steroid
exposure contributes to the remodeling of the GH axis and
defeminization of hepatic steroid-metabolizing enzymes,
which may compromise liver physiology.Mup 1/2/6/8 mRNA expression.
Furthermore, a male predominant liver gene (Cyp2d9) was
not masculinized in TP females either, whereas two female
predominant genes (Cyp2b9 and Cyp2a4) were defeminized.
These data support the hypothesis that neonatal steroid
exposure contributes to the remodeling of the GH axis and
defeminization of hepatic steroid-metabolizing enzymes,
which may compromise liver physiology.Cyp2d9) was
not masculinized in TP females either, whereas two female
predominant genes (Cyp2b9 and Cyp2a4) were defeminized.
These data support the hypothesis that neonatal steroid
exposure contributes to the remodeling of the GH axis and
defeminization of hepatic steroid-metabolizing enzymes,
which may compromise liver physiology.Cyp2b9 and Cyp2a4) were defeminized.
These data support the hypothesis that neonatal steroid
exposure contributes to the remodeling of the GH axis and
defeminization of hepatic steroid-metabolizing enzymes,
which may compromise liver physiology.