Actions of hypoxia on catecholamine synthetic enzyme mRNA expression before and after development of adrenal innervation in the sheep fetus

Adams, Michael Brenton; McMillen, I. Caroline

doi:10.1111/j.1469-7793.2000.00519.x

Cited by 20 publications

(16 citation statements)

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“…Hypoxia is a potent fetal stressor, and the effect of experimentally induced, acute (min to hours), prolonged (several hours to days), or chronic (a few weeks) hypoxia on fetal plasma catecholamine concentrations and catecholamine synthesis has been examined (2,20,38). In addition to the duration, the severity has varied greatly among the various paradigms employed to induce hypoxia.…”

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confidence: 99%

Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus

Ducsay¹,

Hyatt²,

Młynarczyk³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Ducsay CA, Hyatt K, Mlynarczyk M, Root BK, Kaushal KM, Myers DA. Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus. Am J Physiol Regul Integr Comp Physiol 293: R1997-R2005, 2007. First published August 15, 2007; doi:10.1152/ajpregu.00313.2007.-We previously communicated that long-term hypoxia (LTH) resulted in a selective reduction in plasma epinephrine following acute stress in fetal sheep. The present study tested the hypothesis that LTH selectively reduces adrenomedullary expression of phenylethanolamine-N-methyltransferase (PNMT), the rate-limiting enzyme for epinephrine synthesis. We also examined the effect of LTH on adrenomedullary nicotinic, muscarinic, and glucocorticoid receptor (GR) expression. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dGA); adrenomedullary tissue was collected from LTH and age-matched, normoxic control fetuses at 139 -141 dGA. Contrary to our hypothesis, in addition to PNMT, adrenomedullary expression (mRNA, protein) of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were reduced in the LTH fetus. Immunocytochemistry indicated that TH and DBH expression was lower throughout the medulla, while PNMT appeared to reflect a reduction in PNMT-expressing cells. Nicotinic receptor alpha 1, 2, 3, 5, 6, 7, beta 1, 2, and 4 subunits were expressed in the medulla of LTH and control fetuses. Messenger RNA for alpha 1 and 7 and beta 1 and 2 subunits was lower in LTH fetuses. Muscarinic receptors M1, M2, and M3 as well as the GR were also expressed, and no differences were noted between groups. In summary, LTH in fetal sheep has a profound effect on expression of key enzymes mediating adrenomedullary catecholamine synthesis. Further, LTH impacts nicotinic receptor subunit expression potentially altering cholinergic neurotransmission within the medulla. These findings have important implications regarding fetal cardiovascular and metabolic responses to stress in the LTH fetus. adrenal; ovine; catecholamine BY LATE GESTATION IN THE DEVELOPING ovine fetus, stress activates the sympathetic nervous system, eliciting the release of both norepinephrine and epinephrine. These catecholamines play an essential role in regulating fetal cardiovascular and metabolic responses to a wide variety of stresses and are fundamental in the adaptation of the neonate to the extrauterine environment postbirth (12,35,36). As observed in the adult, the adrenal medulla is the major source of both basal and stress-induced epinephrine in the circulation and contributes significantly to plasma norepinephrine concentrations in the late-gestation ovine fetus (12,25,34,35). There is evidence that both structural and functional innervation of the adrenal medulla occurs during the final third of gestation as the fetus prepares for birth with synapses between splanchnic cholinergic nerve terminals and adrenal chromaffin cells developing between 100 and 130 days of gestation (dGA; term is ϳ148 dGA) in fetal sheep ...

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confidence: 99%

Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus

Ducsay¹,

Hyatt²,

Młynarczyk³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In the adrenal gland, a negative or positive mod-ulation related to stages of development and to effectiveness or not of innervation has been described for the catecholamine-synthesizing enzymes and for catecholamines themselves. Adams and McMillen [37] observed a decrease in the relative expression of adrenal TH mRNA at 20 h after exposure to hypoxia in sheep fetuses aged 96-105 days, i.e. before the development of adrenal innervation.…”

Section: Discussionmentioning

confidence: 99%

Age-Related Modulation of Dopamine D1 Receptor mRNA Level by Hypoxia in Rabbit Adrenal Gland

Labaune¹,

Boutroy²,

Bairam³

2003

Neonatology

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In the perinatal period, the fetus and the neonate may be exposed to hypoxic conditions. The adrenal gland responds to systemic hypoxia by releasing catecholamines. Dopamine and dopamine D1 receptor are present in the adrenal medulla and are liable to be affected by exposure to hypoxia. We used a rabbit model to determine whether hypoxia modulates the dopamine D1 receptor (DA D1-R) mRNA expression in adrenal glands during development. Rabbits were investigated according to four different hypoxic conditions: 15% O₂ for 6 h, 15% O₂ for 24 h, 8% O₂ for 6 h, and 8% O₂ for 24 h. Control groups were maintained in normoxic conditions (21% O₂). For each O₂ condition, animals were studied at three different ages: 1-day old newborns, 25-day-old pups, and 6-month-old adults. We compared the hypoxic groups to their respective age normoxic group. We have shown that hypoxia decreases DA D1-R mRNA expression level, evaluated using Northern blot analysis, in newborn rabbits, whatever the duration and severity of hypoxia. This downmodulation was not observed in 25-day-old and in adult rabbits. This age-related modulation of adrenal DA D1-R mRNA could be linked to the age-related transition from the non-neurogenic to the neurogenic regulation of the adrenal function.

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“…33 Circulating chemical signals associated with states such as hypoxemia or hypoglycemia also can directly stimulate adrenal catecholamine receptors, specifically, dopamine receptors (DA-Rs), until sympathetic innervation reaches complete maturity, several days or even weeks after birth. 34,35 The difference in developmental patterns observed in the striatum compared with the adrenal glands should be underlined. In striatum, DA-R mRNA expression increases from birth to 25 days after birth, when it is at its highest level.…”

Section: Discussionmentioning

confidence: 99%

Effect of betamethasone on the expression of dopamine D 1 receptor mRNA in the developing rabbit adrenal gland

Labaune¹,

Boutroy²,

Bairam³

2003

Current Therapeutic Research

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Background: Antenatal corticotherapy is widely used to enhance pulmonary fetal maturation in cases in which premature birth is likely. The adrenal gland, which has a key role in controlling fetal and neonatal adaptation, appears to be a target organ of glucocorticoids.Objectives: The aim of this study was first to determine the ontogenic profile of dopamine D 1 receptor (DA D 1 -R) messenger RNA (mRNA) in the rabbit. The effects of antenatal exposure to exogenous corticoids on levels of adrenal DA D 1 -R mRNA expression were examined.Methods: Pregnant rabbits free of any treatment or handling before delivery were chosen for the study of DA D 1 -R mRNA ontogenic profile. For the study of the antenatal exposure to exogenous corticoids, pregnant rabbits were given 2 injections of either betamethasone 0.1 mg/kg or saline 0.1 mL/kg. DA D 1 -R mRNA expression was determined using northern blot analysis at 4 developmental ages: fetus (at 27 days of gestation), 1 day of age, 25 days of age, and adulthood. Rabbits were allocated to their respective group (treated or untreated) depending on maternal treatment (betamethasone or saline, respectively).Results: Four pregnant rabbits were used for the ontogenic-profile group, which comprised 11 fetuses, seven 1-day-old rabbits, four 25-day-old rabbits, and 2 adults. Six other pregnant rabbits received betamethasone; 6 saline. The treated group comprised 12 fetuses, twelve 1-day-old rabbits, four 25-day-old rabbits, and 3 adults. The untreated group comprised 12 fetuses, fifteen 1-dayold rabbits, five 25-day-old rabbits, and 3 adults. DA D 1 -R mRNA was expressed in rabbit adrenal glands from the fetal period to adulthood and this expression was not age dependent. Moreover, antenatal corticotherapy induced a significant increase in respective DA D 1 -R mRNA levels of 20%, 15%, and 8% in treated fetuses, 1-day-old rabbits, and 25-day-old rabbits compared with the untreated groups (P Ͻ 0.003, 0.003, and 0.005, respectively). This increase was not observed in adulthood.

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Actions of hypoxia on catecholamine synthetic enzyme mRNA expression before and after development of adrenal innervation in the sheep fetus

Cited by 20 publications

References 45 publications

Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus

Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus

Age-Related Modulation of Dopamine D1 Receptor mRNA Level by Hypoxia in Rabbit Adrenal Gland

Effect of betamethasone on the expression of dopamine D 1 receptor mRNA in the developing rabbit adrenal gland

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