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The effects of estradiol-17° infusion into fetal sheep in late gestation

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Abstract

Activation of the hypothalamic-pituitary-adrenal (HPA) axis of fetal sheep during late gestation is associated with increases in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and ultimately results in parturition. However, the mechanisms contributing to the concurrent increases in ACTH and cortisol are unclear. Plasma estradiol-17β (E2) concentrations increase progressively in the prepartum ovine fetus, and we hypothesized that E2 may influence HPA activity by affecting either basal and/or hypoxemia-stimulated ACTH release. We examined potential mechanisms, including altered expression of pro-opiomelanocortin (POMC) in fetal pituitary corticotrophs, and changes in corticosteroid binding globulin (CBG) and/or the enzymes 11β hydroxy steroid dehydrogenase (11β HSD)-1 or 11β HSD-2 in liver and placenta, that could alter negative feedback control. We infused fetal sheep at 127 d of gestation with either E2 (100 μg/24 h) or saline for 100 h. Fetal arterial blood samples were collected at 8 h intervals during the infusion of E2 or saline (n=4), for measurement of basal plasma ACTH and cortisol concentrations, as well as plasma corticosteroid binding capacity (CBC). Placenta and fetal liver samples were collected at 100 h for measurement of placental 11 β HSD-1 and 11β HSD-2 mRNA and hepatic CBG and 11β HSD-1 mRNA, by Northern blotting. Fetal pituitary samples were collected for measurement of POMC mRNA byin situ hybridization. In a separate experiment, fetuses were exposed to 2 h of hypoxemia at 75 h of E2 or saline infusion (n=4), and fetal arterial blood samples were collected during the period of hypoxemia for measurement of plasma ACTH and cortisol concentrations. E2 infusion had no effect on basal plasma concentrations of ACTH or total cortisol, or on the stimulated levels of ACTH or total cortisol achieved in response to hypoxemia. Basal fetal pituitary POMC mRNA also did not change significantly with E2 infusion. No significant increases were observed in plasma CBC during E2 administration. However, hepatic CBG and 11β HSD-1 mRNA were significantly elevated in the livers of E2-treated fetuses. Placental 11β HSD-1 mRNA; but not 11β HSD-2 mRNA was increased by E2 treatment. These data do not support a direct effect of exogenous E2 at the level of basal or hypoxemia-stimulated ACTH output, but suggest that elevated E2 concentrations may alter the expression of genes encoding proteins implicated in tonic regulation of fetal HPA function.

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Authors and Affiliations

  1. Department of Physiology, University of Toronto, Toronto, Ontario

    Sheila Wang, Stephen G. Matthews, Treena M. Jeffray, M. Yvette Stevens & John R. G. Challis

  2. Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario

    Stephen G. Matthews & John R. G. Challis

  3. Department of Physiology, University of Western Ontario, Ontario, Canada

    Sheila Wang, Kaiping Yang & John R. G. Challis

  4. Department of Pharmacology and Toxicology, University of Western Ontario, Ontario, Canada

    Geoffrey L. Hammond

  5. Department of Obstetrics and Gynecology, University of Western Ontario, Ontario, Canada

    Kaiping Yang & Geoffrey L. Hammond

  6. Lawson Research Institute, London, Ontario

    Kaiping Yang & John R. G. Challis

  7. London Regional Cancer Centre, London, Ontario

    Geoffrey L. Hammond

Authors
  1. Sheila Wang
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  2. Stephen G. Matthews
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  3. Treena M. Jeffray
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  4. M. Yvette Stevens
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  6. Geoffrey L. Hammond
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  7. John R. G. Challis
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Correspondence to Sheila Wang.

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Wang, S., Matthews, S.G., Jeffray, T.M. et al. The effects of estradiol-17° infusion into fetal sheep in late gestation. Endocr 6, 271–278 (1997). https://doi.org/10.1007/BF02820503

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  • DOI: https://doi.org/10.1007/BF02820503

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