The Initiation of Fetal Adrenocorticotrophic Activity in the Rat1

Milković, S.; Milković, Karmela; Paunović, Jasna

doi:10.1210/endo-92-2-380

Cited by 80 publications

(39 citation statements)

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“…The naturally occurring changes in progesterone concentrations during the oestrous cycle are sufficiently large to influence MAO activity in various tissues including brain (Kamberi & Kobayashi, 1970;Holzbauer & Youdim, 1972;Youdim, Holzbauer & Woods, 1974). Some measure of the connection between MAO activity and progesterone production was provided by Holzbauer & Youdim (1973) who measured the progesterone content of ovaries and adrenal glands which synthesize and secrete about equal amounts of progesterone in the rat (Fajer, Holzbauer & Newport, 1971;Holzbauer & Godden, 1974 (Milkovic, Milkovic & Paunovic, 1973;Challis, Heap & Illingworth, 1973) also tend to agree with the present results. Urinary output, and release into the blood steam of both adrenaline and noradrenaline is persistently increased during the last days of pregnancy (Parvez et al, 1973a and b).…”

Section: Discussionsupporting

confidence: 86%

Variation in Activity of Monoamine Metabolizing Enzymes in Rat Liver During Pregnancy

Parvez

Youdim

1975

British J Pharmacology

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I Catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) activities in rat liver were measured during pregnancy, parturition and postpartum. Compared with activity in non-pregnant controls, both enzymes showed a significant decrease in activity which was most pronounced at day 18.2 The metabolism of intravenously infused [3 HI -adrenaline to [3HI -metanephrine and to [3 HI -acidic metabolites was also significantly depressed during pregnancy but had returned to control values by the 21 st day. 3 The effects of reserpine and/or nialamide on hepatic COMT and MAO were studied in control and 20-day-pregnant rats. Their action on COMT activity differed in the two groups. MAO was inhibited to a similar extent in these groups whether the drugs were given separately or in combination. 4 It seems possible that the changes in endocrine function which occur during pregnancy are responsible for the observed alterations in enzyme activity.

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Section: Discussionsupporting

confidence: 86%

Variation in Activity of Monoamine Metabolizing Enzymes in Rat Liver During Pregnancy

Parvez

Youdim

1975

British J Pharmacology

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“…Twenty four timemated Sprague-Dawley dams (250 -350 g) were obtained from Hilltop Laboratories on gestation day (GD) 4. It is not likely that maternal stress resulting from transportation affected fetal HPA axis programming, as this axis does not begin to develop until GD 12 or 13 (31,55). In addition, pregnant dams had more than 1 wk of acclimatization before DEX treatment.…”

Section: Methodsmentioning

confidence: 99%

Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

Shoener¹,

Baig²,

Page³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

101

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Glucocorticoids are essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity; however, recent studies warn that exposure to excess endogenous or synthetic glucocorticoid during a specific period of prenatal development adversely affects HPA axis stability. We administered dexamethasone (DEX) to pregnant rats during the last week of gestation and investigated subsequent HPA axis regulation in adult male offspring in unrestrained and restraint-stressed conditions. With the use of real-time PCR and RIA, we examined the expression of regulatory genes in the hippocampus, hypothalamus, and pituitary, including corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), glucocorticoid receptors (GR), mineralcorticoid receptors (MR), and 11-␤-hydroxysteroid dehydrogenase-1 (11␤-HSD-1), as well as the main HPA axis hormones, adrenal corticotropic hormone (ACTH) and corticosterone (CORT). Our results demonstrate that the DEX-exposed group exhibited an overall change in the pattern of gene expression and hormone levels in the unrestrained animals. These changes included an upregulation of CRH in the hypothalamus, a downregulation of MR with a concomitant upregulation of 11␤-HSD-1 in the hippocampus, and an increase in circulating levels of both ACTH and CORT relative to unrestrained control animals. Interestingly, both DEX-exposed and control rats exhibited an increase in pituitary GR mRNA levels following a 1-h recovery from restraint stress; however, the increased expression in DEX-exposed rats was significantly less and was associated with a slower return to baseline CORT compared with controls. In addition, circulating levels of ACTH and CORT as well as hypothalamic CRH and hippocampal 11␤-HSD-1 expression levels were significantly higher in the DEX-exposed group compared with controls following restraint stress. Taken together, these data demonstrate that late-gestation DEX exposure in rats is associated with persistent changes in both the modulation of HPA axis activity and the HPA axis-mediated response to stress. mineralcorticoid receptor:glucocorticoid receptor balance; 11-␤-hydroxysteroid dehydrogenase-1; circadian rhythm; restraint stress A CONSIDERABLE BODY OF EVIDENCE indicates that the limbic system is a central modulator of hypothalamic-pituitary-adrenal (HPA) axis activity (18,41) and that it is exquisitely sensitive to fluctuations in circulating corticosteroids (27,28,56). Corticosteroid receptors, which include both mineralcorticoid receptors (MR) and glucocorticoid receptors (GR), are highly expressed in this system (29,44) and are colocalized in distinct regions, particularly the hippocampus (51, 53). In contrast, nonlimbic sites, such as the prefrontal cortex, hypothalamus, and pituitary, express predominantly GR (10, 43).

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“…Maternal adrenalectomies were performed on 17-daygestation pregnant rats as described by Milkovic et al [25]. Briefly, the animals were anesthetized with ether and two lateral incisions were made through the peritoneum of the back on either side of the spinal cord.…”

Section: Maternal Adrevialectomiesmentioning

confidence: 99%

Metallothionein Synthesis in Foetal, Neonatal and Maternal Rat Liver

et al. 1983

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The synthesis of hepatic metallothionein relative to other cytosol proteins was measured by [35S]cysteine incorporation in foetal, neonatal and pregnant rats. The relative rate of hepatic metallothionein synthesis reached a maximum in foetal liver on days 18 -21 of gestation. Metallothionein synthesis then declined until weaning, when adult levels were established. The rate of metallothionein synthesis was greater in pregnant rats at term than in nulliparous rats.To determine if circulating inducing agents could play a role in the regulation of metallothionein synthesis in foetal liver we treated pregnant rats with inducers at a time prior to the normal rise in foetal liver metallothionein synthesis. Injections of copper, cadmium or hydrocortisone to 17-day-pregnant dams failed to induce foetal metallothionein synthesis. In contrast, zinc injection to the dam was an effective inducer in the foetuses.Maternal laparotomy (performed to expose the foetus for direct injection of inducers) induced foetal metallothionein synthesis. Metallothionein synthesis in the livers of 17-day-gestation dams was induced by all metal injections and laparotomy but, surprisingly, not by hydrocortisone injection. Maternal adrenalectomy did not influence the subsequent normal elevation in foetal or maternal metallothionein synthesis. These results, in conjunction with previous reports, suggest that mobilization of zinc in serum during late gestation may regulate foetal and maternal changes in metallothionein synthesis.Metallothioneins are low-molecular-weight, cysteine-rich proteins normally found in association with Zn2 Metallothioneins have been found in increased concentration, relative to adults, in foetal and neonatal rat liver 211. Porter [22] has demonstrated that 'neonatal mitochondrocuprein', a coppercontaining high-molecular-weight complex in the particulate fractions of foetal bovine liver is, in fact, a polymeric form of metallothionein. The large amounts of metallothionein present in these early developmental stages correlate with increased copper and zinc concentrations in the liver. Such elevated concentrations of metallothionein, binding copper and zinc in foetal and neonatal liver, suggest that this protein may play an important role in metal storage or transport during development [23]. We now report increased levels of metallothionein biosynthesis in rat liver during both foetal and neonatal development. We also report on the inducibility of hepatic metallothionein in response to varying metal, hormone, and/or physiological conditions in rat pups and dams during these developmental stages. MATERIALS A N D METHODS MaterialsMaterials were obtained from the following sources : Tris, hydrocortisone sodium succinate, hydrocortisone, and Sephadex G-75 were from Sigma; [35S]cystine (427 Ci/mmol and lo9Cd (chloride salt, carrier-free) were from New England Nuclear; sucrose and guanidine/HCl were from Schwarz Mann; 2-mercaptoethanol was from Fisher; 5,5'-dithiobis-(2-nitrobenzoic acid) was from Aldrich; cadmium chloride was ...

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The Initiation of Fetal Adrenocorticotrophic Activity in the Rat1

Cited by 80 publications

References 0 publications

Variation in Activity of Monoamine Metabolizing Enzymes in Rat Liver During Pregnancy

Variation in Activity of Monoamine Metabolizing Enzymes in Rat Liver During Pregnancy

Prenatal exposure to dexamethasone alters hippocampal drive on hypothalamic-pituitary-adrenal axis activity in adult male rats

Metallothionein Synthesis in Foetal, Neonatal and Maternal Rat Liver

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