Effects of neonatally administered monosodium glutamate on the sexually dimorphic profiles of circulating growth hormone regulating murine hepatic monooxygenases

Growth hormone was secreted in sexually dimorphic patterns in both 65- and 150-day-old rats (i.e., "on-off" pulsatile for males and "continuous" pulsatile for females), but as a result of a 200-400% increase in pulse levels the mean concentration of hormone in the circulation was about two times as great in the younger animals. Neonatal exposure to phenobarbital at anticonvulsant therapeutic doses for the rat reduced the pulse amplitudes of circulating growth hormone in both the 65- and 150-day-old males but only in the 65-day-old females. As expected, neonatal administration of the barbiturate produced an almost immediate increase in the activities of the hepatic monooxygenases, as measured by hexobarbital metabolism, which declined to noninduction levels after treatment ceased. Contrary to the well-known transient effects of phenobarbital, at around the time of sexual maturity when gender-dependent differences in hepatic monooxygenases appear (males > females), we observed a second "round" of enzyme induction that persisted in both sexes for the remainder of the study (180 days). Because growth hormone is the primary regulator of sex-dependent hepatic monooxygenases, we have proposed that the abnormal plasma growth hormone profiles produced by neonatal phenobarbital are responsible for the permanent induction of hepatic monooxygenases.

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Growth Hormone Pretranslationally Regulates the Sexually Dimorphic Expression of the Prolactin Receptor Gene in Rat Liver

Molecular Endocrinology ◽

10.1210/mend-4-8-1235 ◽

1990 ◽

Vol 4 (8) ◽

pp. 1235-1239 ◽

Cited By ~ 18

Author(s):

John A. Robertson ◽

Lars-Arne Haldosén ◽

Timothy J. J. Wood ◽

Maureen K. Steed ◽

Jan-Åke Gustafsson

Keyword(s):

Growth Hormone ◽

Rat Liver ◽

Receptor Gene ◽

Prolactin Receptor ◽

Sexually Dimorphic ◽

Sexually Dimorphic Expression ◽

Prolactin Receptor Gene ◽

Dimorphic Expression

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Growth Hormone-Dependent and -Independent Sexually Dimorphic Regulation of Phenobarbital-Induced Hepatic Cytochrome P450 2B1 and -2B2

Archives of Biochemistry and Biophysics ◽

10.1006/abbi.1994.1304 ◽

1994 ◽

Vol 312 (1) ◽

pp. 234-239 ◽

Cited By ~ 31

Author(s):

B.H. Shapiro ◽

N.A. Pampori ◽

D.P. Lapenson ◽

D.J. Waxman

Keyword(s):

Growth Hormone ◽

Cytochrome P450 ◽

Sexually Dimorphic ◽

Hepatic Cytochrome

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Opposing Roles of Peroxisome Proliferator-activated Receptor α and Growth Hormone in the Regulation of CYP4A11 Expression in a Transgenic Mouse Model

Journal of Biological Chemistry ◽

10.1074/jbc.m902074200 ◽

2009 ◽

Vol 284 (24) ◽

pp. 16541-16552 ◽

Cited By ~ 23

Author(s):

Üzen Savas ◽

Daniel E. W. Machemer ◽

Mei-Hui Hsu ◽

Pryce Gaynor ◽

Jerome M. Lasker ◽

...

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Transgenic Mice ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Peroxisome Proliferator ◽

Sexually Dimorphic ◽

Peroxisome Proliferator Activated Receptor ◽

Liver And Kidney

CYP4A11 transgenic mice (CYP4A11 Tg) were generated to examine in vivo regulation of the human CYP4A11 gene. Expression of CYP4A11 in mice yields liver and kidney P450 4A11 levels similar to those found in the corresponding human tissues and leads to an increased microsomal capacity for ω-hydroxylation of lauric acid. Fasted CYP4A11 Tg mice exhibit 2–3-fold increases in hepatic CYP4A11 mRNA and protein, and this response is absent in peroxisome proliferator-activated receptor α (PPARα) null mice. Dietary administration of either of the PPARα agonists, fenofibrate or clofibric acid, increases hepatic and renal CYP4A11 levels by 2–3-fold, and these responses were also abrogated in PPARα null mice. Basal liver CYP4A11 levels are reduced differentially in PPARα−/− females (>95%) and males (<50%) compared with PPARα−/+ mice. Quantitative and temporal differences in growth hormone secretion are known to alter hepatic lipid metabolism and to underlie sexually dimorphic gene expression, respectively. Continuous infusion of low levels of growth hormone reduced CYP4A11 expression by 50% in PPARα-proficient male and female transgenic mice. A larger decrease was observed for the expression of CYP4A11 in PPARα−/− CYP4A11 Tg male mice to levels similar to that of female PPARα-deficient mice. These results suggest that PPARα contributes to the maintenance of basal CYP4A11 expression and mediates CYP4A11 induction in response to fibrates or fasting. In contrast, increased exposure to growth hormone down-regulates CYP4A11 expression in liver.

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