Neonatal phenobarbital-induced defects in age- and sex-specific growth hormone profiles regulating monooxygenases

1995 ◽  
Vol 268 (3) ◽  
pp. E439-E445 ◽  
Author(s):  
A. K. Agrawal ◽  
N. A. Pampori ◽  
B. H. Shapiro

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.

1965 ◽  
Vol 49 (1) ◽  
pp. 1-16 ◽  
Author(s):  
M. Apostolakis

ABSTRACT A method for the extraction of prolactin from human pituitary glands is described. It is based on acetone drying, distilled water extraction, acetone and isoelectric precipitation. Two main products are obtained: Fraction R8 with a mean prolactin activity of 12.2 IU/mg and fraction U8 with a mean prolactin activity of 8.6 IU/mg. The former fraction does not contain any significant gonadotrophin activity and the latter contains on an average 50 HMG U/mg. In both cases contamination with ACTH and MSH is minimal. The growth hormone activity of both these fractions is low. It is postulated that in man too, prolactin and growth hormone are two distinct hormones. A total of 1250 human pituitary glands have been processed by this method. The mean prolactin content per pituitary gland has been found to be 73 IU.


1974 ◽  
Vol 75 (1) ◽  
pp. 50-63 ◽  
Author(s):  
Kristian F. Hanssen

ABSTRACT Twenty newly diagnosed, but as yet untreated patients of both sexes with classical juvenile diabetes were investigated by determining the mean plasma immunoreactive growth hormone (IRHGH) and urinary IRHGH for a 24 hour period before and during initial insulin treatment. The plasma IRHGH was significantly higher (0.05 > P > 0.01) before than during initial insulin treatment. During initial insulin treatment, the mean plasma IRHGH was significantly higher (0.01 > P > 0.001) than in a control group. The urinary IRHGH was significantly higher (0.01 > P > 0.001) before than during insulin treatment. The increased urinary IRHGH observed before insulin treatment is thought to be partly due to a defective renal tubular reabsorption of growth hormone. No significant correlation was found between the mean blood sugar and plasma or urinary IRHGH either before or during insulin treatment.


Author(s):  
Armando Félix Quiñonez ◽  
Guillermo E Morales Espejel

This work investigates the transient effects of a single subsurface inclusion over the pressure, film thickness, and von Mises stress in a line elastohydrodynamic lubrication contact. Results are obtained with a fully-coupled finite element model for either a stiff or a soft inclusion moving at the speed of the surface. Two cases analyzed consider the inclusion moving either at the same speed as the mean velocity of the lubricant or moving slower. Two additional cases investigate reducing either the size of the inclusion or its stiffness differential with respect to the matrix. It is shown that the well-known two-wave elastohydrodynamic lubrication mechanism induced by surface features is also applicable to the inclusions. Also, that the effects of the inclusion become weaker both when its size is reduced and when its stiffness approaches that of the matrix. A direct comparison with predictions by the semi-analytical model of Morales-Espejel et al. ( Proc IMechE, Part J: J Engineering Tribology 2017; 231) shows reasonable qualitative agreement. Quantitatively some differences are observed which, after accounting for the semi-analytical model's simplicity, physical agreement, and computational efficiency, may then be considered as reasonable for engineering applications.


1969 ◽  
Vol 115 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Olga Greengard

1. The administration of glucagon, cAMP [adenosine 3′,5′-(cyclic)-monophosphate], BcAMP [6-N-2′-O-dibutyryladenosine 3′,5′-(cyclic)-monophosphate] or adrenaline to foetal rats during the last 2 days of gestation evoked the appearance of tyrosine aminotransferase and enhanced the accumulation of glucose 6-phosphatase in the liver. In foetuses 1–2 days younger only BcAMP was effective. After birth liver glucose 6-phosphatase no longer responds to glucagon or BcAMP. Tyrosine aminotransferase is still inducible by these agents in 2-day-old rats, but not in 50-day-old rats. After adrenalectomy of adults glucagon or BcAMP can enhance the induction of the enzyme by hydrocortisone. The results indicate that the ability to synthesize tyrosine aminotransferase and glucose 6-phosphatase when exposed to cAMP develops sooner than the ability to respond to glucagon with an increase in the concentration of cAMP; the responsiveness of enzymes to different hormones changes with age. A scheme illustrating the sequential development of competence in regulating the level of an enzyme is presented. 2. Actinomycin inhibited the effects of glucagon and BcAMP on liver tyrosine aminotransferase and glucose 6-phosphatase in foetal rats. Growth hormone, insulin and hydrocortisone did not enhance the formation of these enzymes. 3. The time-course of accumulation of glucose 6-phosphatase in the kidney is different from that in the liver. Hormones that increase the accumulation in foetal liver do not do so in the kidney of the same foetus or in the livers of postnatal rats.


1990 ◽  
Vol 4 (8) ◽  
pp. 1235-1239 ◽  
Author(s):  
John A. Robertson ◽  
Lars-Arne Haldosén ◽  
Timothy J. J. Wood ◽  
Maureen K. Steed ◽  
Jan-Åke Gustafsson

2009 ◽  
Vol 284 (24) ◽  
pp. 16541-16552 ◽  
Author(s):  
Üzen Savas ◽  
Daniel E. W. Machemer ◽  
Mei-Hui Hsu ◽  
Pryce Gaynor ◽  
Jerome M. Lasker ◽  
...  

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.


Bone Research ◽  
2013 ◽  
Vol 1 (1) ◽  
pp. 85-97 ◽  
Author(s):  
Vandana Singhal ◽  
Brian C. Goh ◽  
Mary L. Bouxsein ◽  
Marie-Claude Faugere ◽  
Douglas J. DiGirolamo

1994 ◽  
pp. 167-192 ◽  
Author(s):  
Richard F. Walker ◽  
Sei-Won Yang ◽  
Ryuji Masuda ◽  
Cheng-Shih Hu ◽  
Barry B. Bercu

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