The origin of cortisol in the blood of fetal sheep

Hennessy, D. P.; Coghlan, John P.; Hardy, Kenneth J.; Scoggins, BA; Wintour, E. M.

doi:10.1677/joe.0.0950071

Cited by 95 publications

(56 citation statements)

References 24 publications

(43 reference statements)

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“…There was a highly significant correlation between GFR and amount of sodium reabsorbed in both proximal and distal segments. The gradient These were well within the range of values previously reported in this laboratory (19).…”

Section: Resultssupporting

confidence: 90%

Gestational Changes in Renal Responsiveness to Cortisol in the Ovine Fetus

1989

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ABSTRACT. The ontogenetic renal responsiveness to exogenous cortisol was examined in the chronically cannulated ovine fetus. The contribution of effects a t proximal and distal tubule of the kidney were studied also. Cortisol (81.5 pg/h) was infused into immature ovine fetuses (mean gestational age -113.9 days) on five occasions and increased blood cortisol from 0.8 f 0.5 to 21.3 + 6.2 nmol/ liter. This dose of cortisol produced a highly significant diuresis and natriuresis, in part due to an increase in GFR and in part due to a significant decrease in proximal tubular reabsorption of sodium. Cortisol (107.2 + 4.7 &h) was infused into mature fetuses (mean gestational age 133.4 days) and produced an increase in blood cortisol concentration from 11.4 + 5.6 to 33.7 2 6.8 nmol/liter. No natriuresis or diuresis was seen in the mature fetuses. Cortisol caused a significant depression of proximal tubular sodium reabsorption in mature fetuses, but this extra load was reabsorbed in the distal tubule in these fetuses. The inability of the premature or very low birth wt baby to maintain normal sodium balance on a standard salt intake may be due, at least in part, to a "fetal" renal response to the high plasma cortisol concentrations found in such babies. As the kidney matures it becomes capable of increasing distal tubular sodium reabsorption to compensate for any increased distal tubular fluid delivery. (Pediatr Res 26: 6-10, 1989) Abbreviations FRN,, fractional reabsorption of sodium FR,,i, fractional reabsorption of lithium uN,,v, uKV, UclV, Uc.V, renal excretion rate of sodium/ potassium/chloride/calcium may be responsible for neonatal hyponatremia. However, subsequent investigations have shown that a characteristic of this defect is decreased proximal tubule reabsorption of sodium (2) implying that renal insensitivity to aldosterone may be only partially responsible. The relative immaturity of renal function in very low birth wt and premature neonates seems to be important in the pathogenesis of hyponatremia. Premature neonates exhibit a greater natriuresis and a lower GFR in response to oral salt loading when compared to full-term neonates (5, 6). This is consistent with histopathologic studies that show that glomerular formation in the human infant is not complete until late in gestation (7), whereas tubular development is not complete until 1 y after birth (8).In mature mammals the presence of adrenal steroids is essential for normal renal function. A characteristic of adrenalectomized or hypophysectomized animals and patients with adrenal or pituitary insufficiency is a delayed diuresis following oral or parenteral water loading, accompanied by impaired sodium conservation and reduced GFR and renal blood flow. Administration of deoxycortisone acetate or aldosterone in the presence of normal sodium balance and extra-cellular volume has no effect on the delayed diuresis, whereas cortisol-like steroids correct this diuresis (9-1 1).Clinical investigations have reported that premature neonates have higher plasma co...

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Section: Resultssupporting

confidence: 90%

Gestational Changes in Renal Responsiveness to Cortisol in the Ovine Fetus

1989

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“…These findings are consistent with previous studies that showed reduced placental 11 -HSD2 gene expression in sheep and rats during conditions such as maternal undernutrition which raise glucocorticoid concentrations in utero (Langley-Evans et al 1996, Bertram et al 2001. Indeed, cortisol-induced downregulation of placental 11 -HSD2 activity could explain, at least in part, the lower transplacental passage of cortisol from ewe to fetus observed during late gestation when fetal cortisol levels are reduced by fetal adrenalectomy (Hennessy et al 1982). In contrast to the placenta, cortisol administration had no effect on 11 -HSD2 activity in fetal ovine kidneys.…”

Section: Discussionsupporting

confidence: 92%

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol

Clarke

Ward²,

Forhead³

et al. 2002

Journal of Endocrinology

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The effect of fetal cortisol on the activity of the type 2 isoform of the enzyme, 11 -hydroxysteroid dehydrogenase (11 -HSD2), was examined in ovine placenta and fetal kidney by measuring tissue 11 -HSD2 activity during late gestation when endogenous fetal cortisol levels rise and after exogenous cortisol administration to immature fetuses before the prepartum cortisol surge. Placental 11 -HSD2 activity decreased between 128-132 days and term (]145 days of gestation) in association with the normal prepartum increase in fetal plasma cortisol. Raising fetal cortisol levels to prepartum values in the immature fetus at 128-132 days of gestation reduced placental 11 -HSD2 activity to term values. In contrast, 11 -HSD2 activity in the fetal renal cortex was unaffected by gestational age or cortisol infusion. When all the data were combined, there was an inverse correlation between the log fetal plasma cortisol level at delivery and placental 11 -HSD2 activity, expressed both on a weight-specific basis and per mg placental protein.Fetal cortisol therefore appears to be a physiological regulator of placental, but not renal, 11 -HSD2 activity in fetal sheep during late gestation. These findings have important implications, not only for glucocorticoid exposure in utero, but also for the local actions of cortisol within the placental tissues that are involved in initiating parturition in the sheep.

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“…In the present study, the fetuses were not instrumented, and therefore fetal plasma concentrations of ACTH and cortisol were not measured, as it is not possible to chronically instrument fetuses before mid-gestation. However, cortisol in fetal sheep comes almost entirely from the mother before GD 122 (Hennessy et al, 1982), and therefore, maternal elevations in cortisol as observed in this study would result in some degree of cortisol elevation in the fetus. These elevations may permanently alter the development and function of the HPA axis, and thus lead to long-term behavioral, cognitive, and immune deficits (Zhang et al, 2005).…”

Section: Discussionmentioning

confidence: 65%

“…Cortisol readily crosses the placenta and maternal cortisol is the chief source of cortisol in the ovine fetus until gestational day 121 (term is 147 days), following which 12 to 40% is derived from the mother (Beitins et al, 1970;Hennessy et al, 1982). Further, alterations in fetal cortisol concentrations by alcohol may also impact on fetal thyroid hormone concentrations (Forhead et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Maternal adrenocorticotropin, cortisol, and thyroid hormone responses to all three-trimester equivalent repeated binge alcohol exposure: ovine model

Ramadoss

Tress

Chen

et al. 2008

Alcohol

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Alcohol-mediated alterations in hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitarythyroid (HPT) axis function are two proposed mechanisms by which alcohol causes neurodevelopmental injury to the fetus. We previously reported that third trimester-equivalent only alcohol exposure in sheep results in increases in the maternal and fetal adrenocorticotropin (ACTH) and cortisol levels, and decreases in the fetal thyroid hormones T 3 and T 4 and maternal T 3 levels. In this study, we wished to characterize the maternal HPA and HPT hormone responses to repeated binge alcohol exposure during all three trimester-equivalents of pregnancy in sheep. Pregnant ewes received intravenous infusions of alcohol at doses of 0.75, 1.25 or 1.75 g/kg over 1 hour with mean peak blood alcohol concentrations of 90, 126 or 183 mg/dl respectively on three consecutive days each week beginning on gestation day (GD) 4. Maternal blood samples were collected on GDs 6, 40, 90, and 132. Maternal plasma concentrations of ACTH and cortisol increased in response to the high alcohol dose, and the magnitude of these elevations was not different across gestation. Thyroid hormone levels were not different when comparing among treatment groups at any time point during gestation. However, there was an ontogenetic decrease in the maternal T 3 concentration beginning between GDs 6 and 40 and a decrease in maternal T 4 and free T 4 beginning between GDs 40 and 90. The current findings suggest that: 1) maternal alcohol consumption at any time during gestation stimulates the HPA axis, 2) maternal HPA responsiveness to alcohol does not change across gestation, 3) binge alcohol exposure at these doses lasting all three trimester equivalent of human brain development does not reduce maternal thyroid hormone concentration, 4) alterations in fetal thyroid function in response to alcohol exposure do not occur as a result of diminished maternal thyroid hormone contribution, and 5) there is an ontogenetic decrease in ovine maternal thyroid hormones over gestation.

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The origin of cortisol in the blood of fetal sheep

Cited by 95 publications

References 24 publications

Gestational Changes in Renal Responsiveness to Cortisol in the Ovine Fetus

Gestational Changes in Renal Responsiveness to Cortisol in the Ovine Fetus

Regulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in ovine placenta by fetal cortisol

Maternal adrenocorticotropin, cortisol, and thyroid hormone responses to all three-trimester equivalent repeated binge alcohol exposure: ovine model

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