Regulation of erythropoietin gene expression in fetal sheep by glucocorticoids.

Abstract

Erythropoietin (Epo) gene expression in ovine fetal liver and kidneys was measured by competitive RT-PCR in situations in which fetal glucocorticoid status was altered. Bilateral adrenalectomy at 120 +/- 0.3 days gestation (term is 145-150 days) caused a significant (P < 0.05) 5-fold increase in renal Epo messenger RNA (mRNA) levels at 145 +/- 1 days compared to those in age-matched controls. With cortisol replacement in adrenalectomized fetuses, renal Epo mRNA levels dropped to 17% of this values (P < 0.05). Cortisol infusion (230 micrograms/h for 48 h) at 108 +/- 1 day decreased renal Epo gene expression significantly (P < 0.01) to 23% of the control value; dexamethasone treatment of the ewe at midgestation (0.76 mg/h for 48 h) also decreased fetal, but not adult, renal Epo mRNA levels (to 12% of control value; P < 0.01). Fetal and maternal liver Epo mRNA levels were unaffected by glucocorticoid status at any stage of pregnancy. Thus, glucocorticoids can influence fetal renal, but not maternal, Epo gene expression. In the presence of high concentrations of fetal glucocorticoids, plasma Epo values were consistently 4-5 mU/ml, close to the sensitivity of the assay, whereas in seven adrenalectomized fetuses, the plasma Epo value was 9.1 +/- 1.4 mU/ml.

Ovine AQP 1 : cDNA cloning, ontogeny, and control of renal gene expression

“…Glucocorticoid treatment alters fibronectin expression in term but not first-trimester human placenta [30]. Glucocorticoid treatment also decreased the expression of the erythropoietin gene in the liver of ovine fetuses at 60 but not at 75 days of gestation [31,32].…”

“…The denatured RNA was then transferred to Hybond-C Super (Amersham Life Sciences, Buckinghamshire, England, UK) membranes by capillary elution. Filters were baked at 80° C for 2 h to fix the RNA and then prehybridized for at least 1 h. The ovine cDNA was labelled with [alpha 32 P] dCTP (3000 Ci/mmol, 1 Ci=37 gbq, NEN Research Products, Boston, Mass., USA). The filters were then hybridized overnight at 65° C in 5×SSC, 5× Denhardt's reagent (0.02% polyvinylpyrrolidone/0.02% Ficoll/0.02% bovine serum albumin), 1 mM Na 2 ED-TA, 1% sodium dodecyl sulfate (SDS), and 100 µg/ml heat-denatured salmon sperm DNA (all reagents from Sigma).…”

Hormones as epigenetic signals in developmental programming

“…In sheep, the metabolic, endocrine and cardiovascular responses to hypoxaemia are altered by administration of dexamethasone to either the mother or the fetus (Fletcher et al 2003;Jellyman et al 2004a,b). Glucocorticoids prolong the bradycardic response, increase the femoral vasoconstrictor response and enhance the increments in plasma neuropeptide Y, glucose and lactate to hypoxaemia Fowden et al (1993) ↑ Argininosuccuate lipase, ↑ 11βHSD1 Renouf et al (1995); Sloboda et al (2002) ↑ GH & prolactin receptors Li et al (1996); Phillips et al (1997) ↓ AT 1 receptors Segar et al (1995) ↑ IGF-I, ↓ IGF-II gene expression Li et al (1996), (1998) ↑ CBG, ↑ IGFBP, ↑ erythropoietin Lim et al (1996) ↓ Angiotensinogen gene expression Olson et al (1991); Segar et al (1995) ↑ Deiodinase type 1 Forhead et al (2006Forhead et al ( , 2007 ↑ Glycogen deposition Barnes et al (1978); Klepac, (1985) during the period of steroid exposure (Fletcher et al 2000b(Fletcher et al , 2003Jellyman et al 2005). Some but not all of these effects persist after treatment (Fletcher et al 2003;Jellyman et al 2005).…”

“…In some tissues, maternal glucocorticoid administration has opposite effects in the fetus and adult offspring (Table 2). In sheep, for instance, prenatal glucocorticoid overexposure reduces hepatic production of angiotensinogen and corticosteroid‐binding globulin in the fetus but enhances their production in adult liver in a sex‐linked manner (Olson et al 1991; Lim et al 1996; O’Regan et al 2004; Sloboda et al 2005). Some of the consequences of prenatal hormone exposure do not become apparent until after birth.…”

Erythropoietin response after correction of severe hypoxaemia due to acute respiratory failure in chronic obstructive pulmonary disease patients

“…Fenoterol, a selective β 2 -adrenoceptor agonist, increases EPO concentration, although this same effect is not associated with the inhalation of high doses of salbutamol [25,26]. It has also been reported [27] that glucocorticoids can influence fetal renal (but not maternal) EPO gene expression in experimental animals, but their therapeutic value and the impact on EPO synthesis is still unclear. For example, it is known that dexamethasone may cause a reduction in the secretion of EPO-inhibitory cytokines from monocytes [28].…”