Multihormonal Control of Microsomal 5α-Reductase Activity in Cultured Adult Female Rat Hepatocytes*

Endocrinology ◽  
1982 ◽  
Vol 111 (1) ◽  
pp. 136-143 ◽  
Author(s):  
MARGARET ANN MILLER ◽  
ANTONIO E. COLAS
1985 ◽  
Vol 106 (1) ◽  
pp. 71-79 ◽  
Author(s):  
R. C. K. Pak ◽  
K. W. K. Tsim ◽  
C. H. K. Cheng

ABSTRACT Hepatic microsomal testosterone 5-reductase activity was approximately fourfold higher in adult female rats than in males. This discrepancy was only partly androgen-dependent since gonadectomy of male rats at 68 days of age resulted in only a partial increase of the enzyme activity. This increase was reversible by the administration of testosterone. Similar treatment, however, produced no effect in the female rat, indicating that there is a sex difference in testosterone responsivity. Castration of newborn male rats resulted in a marked increase in the basal enzyme activity. This increase was not affected by treating the adults with testosterone. Giving testosterone to male rats immediately after neonatal gonadectomy, or to newborn female rats, did not produce the male pattern of both the basal enzyme activity and the testosterone responsivity in adulthood. These results suggest that a brief exposure to neonatal androgen is not critical for the expression of the male type of enzyme activity, but that the continuous presence of the male gonads up to and including the pubertal period is essential. Exposure of pubescent female rats to testosterone during the period from 35 to 50 days of age resulted in a significant increase in testosterone sensitivity when tested at 90 days of age, suggesting that pubertal exposure to androgen is important for the expression of testosterone responsivity in adulthood. The sensitivity was potentiated when the animals were ovariectomized before puberty. Furthermore, the enzyme activity in prepubertally ovariectomized female rats was significantly lower than that in adult gonadectomized animals. The decreased level of activity returned to the control value when oestrogen was replaced during puberty, indicating that peripubertal oestrogen exposure is required for maintaining the high level of activity found in adult female rats. The present findings suggest that the pubertal period represents a sensitive phase during which sex hormones act to regulate the sexual differentiation of testosterone 5-reductase activity in the rat. J. Endocr. (1985) 106, 71–79


2009 ◽  
Vol 19 (11) ◽  
pp. 2719-2727 ◽  
Author(s):  
J.-R. Chen ◽  
Y.-T. Yan ◽  
T.-J. Wang ◽  
L.-J. Chen ◽  
Y.-J. Wang ◽  
...  

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3237-3244 ◽  
Author(s):  
Tamara Blutstein ◽  
Peter J. Baab ◽  
H. Ronald Zielke ◽  
Jessica A. Mong

1991 ◽  
Vol 273 (2) ◽  
pp. 485-488 ◽  
Author(s):  
V A Zammit ◽  
A M Caldwell

The roles of protein kinase C, Ca2+/calmodulin-dependent protein kinase and AMP-activated protein kinase in the phosphorylation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase induced by Ca2(+)-mobilizing conditions in isolated hepatocytes were investigated. Only partial evidence for the involvement of AMP-activated kinase was found. Antagonism of calmodulin action prolonged the decrease in expressed/total activity ratio induced by vasopressin plus glucagon. Protease inhibitors active against Ca2(+)-dependent cytosolic proteases or lysosomal proteolysis did not attenuate the loss of total HMG-CoA reductase induced by glucagon plus vasopressin, but calmodulin antagonists largely prevented this effect.


2011 ◽  
Vol 40 (1) ◽  
pp. 83-92 ◽  
Author(s):  
Meena R. Sharma ◽  
Wojciech Dworakowski ◽  
Bernard H. Shapiro

Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2—which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450—were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host’s liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation.


2018 ◽  
Vol 283 ◽  
pp. 91-99 ◽  
Author(s):  
Wan-xia Zhang ◽  
Yin-ping Li ◽  
Jie Fan ◽  
Hui-jian Chen ◽  
Gai-ling Li ◽  
...  

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