Ontogenesis of Thyroid Function in the Neonatal Rat. Thyroxine (T<sub>4</sub>) and Triiodothyronine (T<sub>3</sub>) Production Rates

Dubois, Jean-Philippe; Dussault, J H

doi:10.1210/endo-101-2-435

Cited by 88 publications

(49 citation statements)

References 22 publications

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“…[5][6][7]13 Increases in maternal plasma hormones occur near the time of birth 29 and conceivably may play a role in the induction of C7␣H in very late fetal animals. The second rise at day 12 and the peak at weaning are coincident with transient high levels of circulating corticosterone in the suckling, [30][31][32] consistent with a role for this hormone in triggering the second rise in C7␣H mRNA. An increase in thyroid hormone at weaning has been described, 29,30,32,33 which may contribute synergistically to the large C7␣H mRNA increase observed at this stage.…”

Section: Discussionmentioning

confidence: 55%

Cholesterol 7α-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development

et al. 1998

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Cholesterol 7␣-hydroxylase is a rate-limiting enzyme in bile acid synthesis, a major pathway for cholesterol catabolism. It plays a crucial role in postnatal development and survival. In an adult liver, its activity and messenger RNA (mRNA) are heterogeneously distributed with concentration in the pericentral area. We defined how the pattern of cholesterol 7␣-hydroxylase mRNA evolves during rat liver development, correlated this with its total liver mRNA levels, and determined when its heterogeneous pattern of expression is established. Cholesterol 7␣-hydroxylase mRNA was undetectable in 18-day-old fetal livers by Northern blot. It was increased markedly in newborns with a homogeneous liver lobular distribution as determined by in situ hybridization. At postnatal day four, mRNA levels were markedly decreased with concomitant appearance of a lobular gradient: mRNA was detected only in a few hepatocytes located around efferent venules. At 22 days, the time of highest mRNA expression, a marked extension of the gradient towards the periportal area was observed, indicating that the increase in total liver cholesterol 7␣-hydroxylase mRNA level was a result of recruitment of hepatocytes upstream from the central vein area. By 28 days, the adult pattern was observed. Thus, expression of cholesterol 7␣-hydroxylase mRNA is tightly regulated during rat liver development, both temporally and spatially supporting its critical role in normal postnatal development.(HEPATOLOGY 1998;28:1064-1072.)Bile acids play a key role in absorption of lipids, including fat-soluble vitamins. Bile acid synthesis represents the major regulated pathway for catabolism and excretion of cholesterol in mammals. The hepatospecific enzyme cholesterol 7␣-hydroxylase (C7␣H; EC 1.14.13.17; CYP7A) catalyzes a rate-limiting step in this important process. [2][3][4] Its activity is tightly regulated in vivo by a number of different effectors acting predominantly at the transcriptional level. C7␣H is modulated by hormones, including thyroxin, glucocorticoids, and insulin 5-7 ; and by dietary factors. [8][9][10] It is regulated in a negative feedback manner by hydrophobic bile acids returning to the liver via the enterohepatic circulation. 11-13 It exhibits a diurnal rhythm, with maximum activity in the dark phase and minimum during the light phase in rats. [13][14][15] The expression of C7␣H in adult rats is tightly regulated spatially along the liver cell plate; the enzymatic activity 16 and mRNA level 17,18 are not distributed uniformly among parenchymal cells; rather, C7␣H is predominantly found in a subgroup of hepatocytes localized around the central vein.Liver cell heterogeneity is considered to be a major determinant for proper execution and regulation of most liver functions. 19,20 It reflects differentiation of hepatocytes within the liver plate, which is established during development. In most cases, it is regulated at the transcriptional level. The role of liver cell heterogeneity in the developmental regulation of bile acid synthesis is unknown....

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Section: Discussionmentioning

confidence: 55%

Cholesterol 7α-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development

et al. 1998

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“…Although both mRNA and protein levels in the organs mentioned reached maximal levels perinatally, it is of interest that for those organs, for which paired samples were available, tissue TRa 2 and TRb 1 protein peaked at 5 days before birth. In contrast, TRa 1 protein follows a similar time course as circulating thyroid hormones (Dubois & Dussault 1977) to reach its highest level after birth. This latter temporal association is in line with the finding that unliganded TRa1 is detrimental to postnatal development (Chassande 2003).…”

Section: Discussionmentioning

confidence: 97%

Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation

Keijzer

Blommaart²,

Labruyère³

et al. 2007

Journal of Molecular Endocrinology

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The perinatal changes in the pattern of expression of the thyroid hormone receptor (TR) isoforms TRa 1 TRa 2 , TRb 1 , and TRb 2 were investigated using in situ hybridization and immunohistochemistry, and RT-PCR and western blotting as visualization and quantification techniques respectively. In liver, lung, and kidney, TRa mRNA was expressed in the stromal and TRb mRNA in the parenchymal component of the tissues. When compared with liver, TRa mRNA concentrations were tenfold higher in lung, kidney, and intestine, and 100-fold higher in brain, with TRa 2 mRNA concentrations exceeding those of TRa 1 5-to 10-fold. Tissue TRb 1 mRNA concentrations were similar in liver, lung, and brain, and 3-to 5-fold higher in kidney and intestine. None of the TRb 2 mRNA could be detected outside the pituitary. Tissue TRa 2 and TRb 1 protein levels reached adult levels at 5 days before birth, whereas TRa 1 protein peaked after birth. Because of the distinct time-course of thyroid hormonebinding receptors TRa 1 and TRb 1 , we speculate that an initiating, TRb 1 -mediated signaling from the parenchyma is followed by a TRa 1 -mediated response in the stroma. When compared with organs with a complementary parenchymal-stromal expression pattern, organs with extensive cellular co-expression of TRa and TRb (brain and intestinal epithelium) were characterized by a very low TRa protein: mRNA ratio, implying a low translational efficiency of TR mRNA or a high turnover of TR protein. The data indicate that the TR-dependent regulatory cascades are controlled differently in organs with a complementary tissue expression pattern and in those with cellular co-expression of the TRa and TRb genes.

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“…The rat is born with an immature hormonal state and the maturation of the pituitary-thyroid axis proceeds during the first 2 wk of postnatal life (13,15). In contrast, this maturational process begins at mid-gestation in the human fetus.…”

Section: H Experiments a Decrease In Plasma Tconcentration Aftermentioning

confidence: 99%

Effect of Caffeine on Thyroid and Pituitary Function in Newborn Rats

et al. 1983

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SummaryThe possibility that caffeine, a central nervous system stimulant used in neonatal apnea, may produce acute or chronic changes in growth hormone (GH), thyroxine (T4) and thyrotropin (TSH) was studied in the newborn rat. Five-day-old rats were separated into three groups: control (0) group receiving saline, Group I (low dose caffeine) receiving 5 mg/kg and Group I1 (high dose caffeine) receiving 50 mg/kg. Acute effects were studied at 2, 4, and 24 h after injection. Chronic effects were studied 24 h after the last of 10 daily injections. GH, T4, and TSH were measured by radioimmunoassay and caffeine by high pressure liquid chromatograph. GH was increased at all times and all doses after a single injection of caffeine. After chronic therapy, the increase in GH was small, suggesting depletion of pituitary reserve. A high dose of caffeine had a biphasic effect on T4 with an increase at 4 h and a decrease at 24 h. Thyrotropin-releasing hormone (TRH)-induced TSH release at 24 h was not influenced by caffeine administration. Chronic caffeine therapy stimulated both T4 and TSH; however, TRH-stimulated TSH release was decreased, suggesting that chronic therapy may blunt pituitary TSH response. AbbreviationsGH, growth hormone PDE, phosphodiesterase T3, triiodothyronine T4, thyroxine TRH, thyrotropin releasing hormone TSH, thyrotropinBesides the stimulant effect of the methylxanthines on the central nervous system and on cardiac inotropy and chronotropy, these compounds exert a variety of hormonal and metabolic effects. The administration of two methylxanthines, caffeine and theophylline, to adult rats results in decreased GH, TSH, TQ and thyroxine T4 serum levels (29). But in in vitro isolated organ preparations, caffeine increases T4 (3) and TSH (28) ) did not find any modification in basal GH after aminophylline, whereas, Ensinck et al. (17) described a decrease in GH serum level. After a low dose of oral caffeine given to adult healthy men, neither GH, TSH nor Tg were modified (30). Because caffeine is currently used in the premature neonate for the treatment of apnea, we evaluated the changes in GH, T4, and TSH after caffeine in the newborn rat. MATERIALS AND METHODSFive-day-old male Sprague-Dawley rats were obtained from the Canadian Breeding Farm, St. Constant, Quebec. Two sets of experiments were respectively designed to evaluate the acute and the chronic effects of caffeine. Each set used three groups: a control group, which received saline; a low dose caffeine group, which received 5 mg/kg of caffeine dissolved in saline; and a high dose caffeine group, which received 50 mg/kg. Caffeine (37) or saline was injected intraperitoneally in a volume of 0.05 ml/rat. Each group consisted of 30-35 rats. In the acute experiment, the animals were sacrificed at various time intervals after a single injection of saline or caffeine: 2, 4, and 24 h. In the chronic experiment, animals were injected daily for a 10 day period. They were sacrificed 24 h after the last injection. The rat pups were kept with their suckling mot...

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Ontogenesis of Thyroid Function in the Neonatal Rat. Thyroxine (T₄) and Triiodothyronine (T₃) Production Rates

Cited by 88 publications

References 22 publications

Cholesterol 7α-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development

Cholesterol 7α-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development

Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation

Effect of Caffeine on Thyroid and Pituitary Function in Newborn Rats

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Ontogenesis of Thyroid Function in the Neonatal Rat. Thyroxine (T4) and Triiodothyronine (T3) Production Rates

Cited by 88 publications

References 22 publications

Cholesterol 7α-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development

Cholesterol 7α-hydroxylase (CYP7A): Patterns of messenger RNA expression during rat liver development

Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation

Effect of Caffeine on Thyroid and Pituitary Function in Newborn Rats

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Ontogenesis of Thyroid Function in the Neonatal Rat. Thyroxine (T₄) and Triiodothyronine (T₃) Production Rates