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Abstract:

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 GHRH-somatostatin-GH 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. © 2010 Society for Endocrinology.

Registro:

Documento: Artículo
Título:Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice
Autor:Ramirez, M.C.; Luque, G.M.; Ornstein, A.M.; Becu-Villalobos, D.
Filiación:Instituto de Biología Y Medicina Experimental-CONICET, Consejo Nacional de Investigaciones Científicas Y Técnicas, Vuelta de Obligado 2490, Buenos Aires 1428, Argentina
Palabras clave:growth hormone; liver protein; messenger RNA; somatostatin; testosterone propionate; androgen therapy; animal experiment; animal tissue; article; body weight; drug activity; female; genome imprinting; hypothalamus; male; mouse; nonhuman; priority journal; protein expression; protein secretion; protein urine level; Animals; Aryl Hydrocarbon Hydroxylases; Body Weight; Cytochrome P-450 Enzyme System; Female; Growth Hormone; Hypothalamus; Insulin-Like Growth Factor I; Liver; Male; Mice; Mice, Inbred C57BL; Pituitary Gland; Prolactin; Proteins; Steroid Hydroxylases; Testosterone; Virilism
Año:2010
Volumen:207
Número:3
Página de inicio:301
Página de fin:308
DOI: http://dx.doi.org/10.1677/JOE-10-0276
Título revista:Journal of Endocrinology
Título revista abreviado:J. Endocrinol.
ISSN:00220795
CODEN:JOENA
CAS:growth hormone, 36992-73-1, 37267-05-3, 66419-50-9, 9002-72-6; somatostatin, 38916-34-6, 51110-01-1; testosterone propionate, 57-85-2; Aryl Hydrocarbon Hydroxylases, 1.14.14.1; CYP2D9 protein, mouse, 1.14.14.1; Cyp2a4 protein, mouse, 1.14.14.1; Cyp2b9 protein, mouse, 1.14.14.1; Cytochrome P-450 Enzyme System, 9035-51-2; Growth Hormone, 9002-72-6; Insulin-Like Growth Factor I, 67763-96-6; Prolactin, 9002-62-4; Proteins; Steroid Hydroxylases, 1.14.-; Testosterone, 58-22-0; major urinary proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00220795_v207_n3_p301_Ramirez

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Citas:

---------- APA ----------
Ramirez, M.C., Luque, G.M., Ornstein, A.M. & Becu-Villalobos, D. (2010) . Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice. Journal of Endocrinology, 207(3), 301-308.
http://dx.doi.org/10.1677/JOE-10-0276
---------- CHICAGO ----------
Ramirez, M.C., Luque, G.M., Ornstein, A.M., Becu-Villalobos, D. "Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice" . Journal of Endocrinology 207, no. 3 (2010) : 301-308.
http://dx.doi.org/10.1677/JOE-10-0276
---------- MLA ----------
Ramirez, M.C., Luque, G.M., Ornstein, A.M., Becu-Villalobos, D. "Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice" . Journal of Endocrinology, vol. 207, no. 3, 2010, pp. 301-308.
http://dx.doi.org/10.1677/JOE-10-0276
---------- VANCOUVER ----------
Ramirez, M.C., Luque, G.M., Ornstein, A.M., Becu-Villalobos, D. Differential neonatal testosterone imprinting of GH-dependent liver proteins and genes in female mice. J. Endocrinol. 2010;207(3):301-308.
http://dx.doi.org/10.1677/JOE-10-0276