-Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice.

RAMIREZ, M.C.; LUQUE, G.M.; ORNSTEIN, A.M. AND BECU-VILLALOBOS

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Año: 2010 vol. 207 p. 301 - 308

0022-0795

Abnormal exposure to steroid hormones within a criticaldevelopmental period elicits permanent alterations in femalereproductive physiology in rodents, but the impact on thefemale GH axis and the underlying sexual differences inhepatic enzymes have not been described in detail. We haveinvestigated the effect of neonatal androgenization of femalemice (achieved by s.c. injection of 100 mg testosteronepropionate (TP) on the day of birth: TP females) on theGHRH–somatostatin–GH axis and downstream GH targets,which included female and male predominant liver enzymesand secreted proteins. At 4 months of age, an organizationaleffect of neonatal testosterone was evidenced on hypothalamicGhrh mRNA level but not on somatostatin (stt)mRNA level. Ghrh mRNA levels were higher in males thanin females, but not in TP females. Increased expression in TPfemales correlated with increased pituitary GH content andsomatotrope population, increased serum and liver IGF-Iconcentration, and ultimately higher body weight. Murineurinary proteins (MUPs) that were excreted at higher levels inmale urine, and whose expression requires pulsatile occupancyof liver GH receptors, were not modified in TP femalesand neither was liver Mup 1/2/6/8 mRNA expression.Furthermore, a male predominant liver gene (Cyp2d9) wasnot masculinized in TP females either, whereas two femalepredominant genes (Cyp2b9 and Cyp2a4) were defeminized.These data support the hypothesis that neonatal steroidexposure contributes to the remodeling of the GH axis anddefeminization of hepatic steroid-metabolizing enzymes,which may compromise liver physiology.