The effects of fetal thyroidectomy during the second trimester in the ovine fetus

Bhakthavathsalan, Amrutha; Mann, Leon; Tang, Lei-Han; Erickson, Noeleen D.; DeLamater, Paul V.; Damm, Christen

doi:10.1016/0002-9378(81)90608-6

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…In fetal sheep, TX results in decreased lung size (4) and functional immaturity at term (13). This is most likely due, in part, to the lack of thyroid hormone stimulation of lung ACE activity, which, in turn, usually facilitates RAS development in preparation for postnatal life (62).…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Chen

Carey

Valego

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward term. At the same time, fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart, and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately before necropsy (ϳ137 dGA), fetuses were infused with isoproterenol and the hemodynamic responses were noted. TX significantly decreased plasma thyroid hormone concentrations and renal renin mRNA and renal active renin levels but did not change fetal plasma active renin levels. TX decreased both angiotensin II receptor subtype 1 (AT1) mRNA and protein levels in kidney and lung but not in the left ventricle. TX also was associated with increased ANG II receptor subtype 2 (AT2) mRNA and protein at the 44-kDa band in kidney, whereas AT2 protein was decreased at the 78-kDa level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late-gestation fetal sheep. renin-angiotensin system; fetus THE RENIN-ANGIOTENSIN SYSTEM (RAS), composed of renin, angiotensinogen, ANG I-converting enzyme (ACE), ANG II, and the ANG II receptor subtypes, plays an important role in regulating fetal growth and development, particularly with respect to the cardiovascular system, and electrolyte homeostatic mechanisms (2,22,48). It is well established that components of the fetal RAS are developmentally regulated and exhibit increased activity in late gestation (12,56,57,63). Changes in expression of the levels of ANG II receptor subtypes 1 and 2 (AT1 and AT2) are opposite, with AT1 mRNA low in early gestation and rising to a plateau later, before increasing rapidly close to term, whereas AT2 expression is highest during midpregnancy and then decreases gradually thereafter (46, 47). Tissue-dependent differences also are apparent (18,40,66). The mechanisms underlying these ontogenic patterns of expression are not clear.In fetal sheep, the changes in components of RAS activity appear temporally related to changes in thyroid hormone concentrations, which are low before 130 -135 days of gestational age (dGA) and then markedly increased toward parturition (19). A similar pattern of change is seen in humans (44). These observations suggest that thyroid hormone may be important in regulating ontogenic changes in renin and ANG II receptors.Thyroid hormone also exerts broad eff...

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Section: Discussionmentioning

confidence: 99%

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Chen

Carey

Valego

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Sheep fetuses thyroidectomised between 80 and 87 days have lower heart rates and blood pressure than intact fetuses later in gestation (Bhakthavathsalan et al 1981, Walker & Schuijers 1989. This may be due to suppression of AII and upregulation of bradykinin activities as well as to changes in the autonomic nervous system (Walker & Schuijers 1989).…”

Section: Discussionmentioning

confidence: 99%

“…In fetal sheep, thyroidectomy causes a reduction in lung but not kidney size at term (Bhakthavathsalan et al 1981). Furthermore, the thyroid hormones are recognised to have an important role in the maturation of the fetal lungs and their preparation for extrauterine life (Kitterman 1984).…”

Section: Discussionmentioning

confidence: 99%

Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term

Forhead¹,

Fowden²

2002

Journal of Endocrinology

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In the sheep fetus, pulmonary and renal concentrations of angiotensin-converting enzyme (ACE) increase towards term in parallel with the prepartum surges in plasma cortisol and tri-iodothyronine (T 3 ). The ontogenic change in pulmonary ACE has been shown to be induced, at least in part, by cortisol but the role of the thyroid hormones is unknown. Therefore, this study investigated the effects of thyroid hormones on tissue ACE concentration in fetal sheep during late gestation. Pulmonary and renal ACE concentrations were measured in sheep fetuses after experimental manipulation of thyroid hormone status by fetal thyroidectomy and exogenous hormone infusion. In intact fetuses, pulmonary and renal ACE concentrations increased between 127-132 and 142-145 days of gestation (term 145 2 days), coincident with the prepartum rises in plasma cortisol and T 3 . The ontogenic increment in pulmonary ACE concentration was abolished when the prepartum surge in T 3 , but not cortisol, was prevented by fetal thyroidectomy. At 143-145 days, ACE concentration in the lungs and kidneys of the thyroidectomised fetuses were both lower than those in the intact fetuses. In intact fetuses at 127-132 days, pulmonary ACE was upregulated by intravenous infusions of either cortisol (2-3 mg/kg per day) or T 3 (8-12 µg/kg per day) for 5 days. Renal ACE was unaffected by cortisol or T 3 infusion. Therefore, thyroid hormones have an important role in the developmental control of pulmonary and renal ACE concentration in the sheep fetus towards term. In addition, the prepartum rise in plasma T 3 appears to mediate, in part, the maturational effect of cortisol on pulmonary ACE concentration.

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“…Thyroid hormones, both independently and in conjunction with adrenal cortical steroids, have been implicated in the growth and maturation of the perinatal lung (Ayromlooi et al, ; Ballard, ). For example, RDS has been described in high proportions of congenitally hypothyroid infants, while thyroidectomy of fetal lambs leads to decreased body and lung weights (Smith et al, ; Bhakthavathsalan et al, ).…”

Section: Lung Functional Developmentmentioning

confidence: 99%

Pre‐ and Postnatal Lung Development: An Updated Species Comparison

Lewin¹,

Hurtt

2017

Birth Defects Research

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The purpose of this review is to give an outline of respiratory tract morphological and functional development with an emphasis on perinatal and postnatal maturational processes. In view of the rising need for qualitative and quantitative data for the development of pediatric pharmaceuticals, a comparison of the human situation to experimental animal models is made, and functional data as well as suitable models for human airway diseases and functional testing are presented. Birth Defects Research 109:1519-1539, 2017. © 2017 Wiley Periodicals, Inc.

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The effects of fetal thyroidectomy during the second trimester in the ovine fetus

Cited by 8 publications

References 15 publications

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Effects of thyroid hormones on pulmonary and renal angiotensin-converting enzyme concentrations in fetal sheep near term

Pre‐ and Postnatal Lung Development: An Updated Species Comparison

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