The Late Effects of Neonatal Hyperthyroidism upon the Hypothalamic-Pituitary-Thyroid Axis in the Rat

Bakke, John L.; Lawrence, Nancy; Wilber, John F.

doi:10.1210/endo-95-2-406

Cited by 43 publications

(32 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this model, the injection of pharmacological doses of T4 (or T3) to rats for 3 to 5 days immediately after birth results in the development of central hypothyroidism in adults. These animals also show an impaired pituitary response to TRH (40,41). Thus, the neo-T4 rat model demonstrates that exposure to inappropriately high levels of THs before the HPT axis is functionally mature results in pituitary and/or hypothalamic abnormalities that affect its regulatory mechanisms and set point.…”

Section: Figurementioning

confidence: 99%

Type 3 deiodinase is critical for the maturation and function of the thyroid axis

Hernández¹,

Martı́nez²,

Fiering³

et al. 2006

Journal of Clinical Investigation

299

249

View full text Add to dashboard Cite

Developmental exposure to appropriate levels of thyroid hormones (THs) in a timely manner is critical to normal development in vertebrates. Among the factors potentially affecting perinatal exposure of tissues to THs is type 3 deiodinase (D3). This enzyme degrades THs and is highly expressed in the pregnant uterus, placenta, and fetal and neonatal tissues. To determine the physiological role of D3, we have generated a mouse D3 knockout model (D3KO) by a targeted inactivating mutation of the Dio3 gene in mouse ES cells. Early in life, D3KO mice exhibit delayed 3,5,3′-triiodothyronine (T3) clearance, a markedly elevated serum T3 level, and overexpression of T3-inducible genes in the brain. From postnatal day 15 to adulthood, D3KO mice demonstrate central hypothyroidism, with low serum levels of 3,5,3′,5′-tetraiodothyronine (T4) and T3, and modest or no increase in thyroid-stimulating hormone (TSH) concentration. Peripheral tissues are also hypothyroid. Hypothalamic T3 content is decreased while thyrotropin-releasing hormone (TRH) expression is elevated. Our results demonstrate that the lack of D3 function results in neonatal thyrotoxicosis followed later by central hypothyroidism that persists throughout life. These mice provide a new model of central hypothyroidism and reveal a critical role for D3 in the maturation and function of the thyroid axis.

show abstract

Section: Figurementioning

confidence: 99%

Type 3 deiodinase is critical for the maturation and function of the thyroid axis

Hernández¹,

Martı́nez²,

Fiering³

et al. 2006

Journal of Clinical Investigation

299

249

View full text Add to dashboard Cite

show abstract

“…Al though the last injection of T4 was given on the 6th day of life, the hyperthyroid stage persisted at least until the 35th day of life. The serial measurements of T4 and TSH in the neonatal hyperthyroid rats have not been reported before although a few studies show these thyroid hormone levels later in life (14,15). Although plasma T4 levels were not significantly different among groups A and B on day 35 of life, the plasma TSH levels were still significantly different.…”

Section: Discussionmentioning

confidence: 85%

“…Pituitary responsiveness to TRH stimulus in neonatal hyperthyroid rats has been done in the past (15,16). In one study (16) intravenous TRH showed a blunted TSH response in neonatal hyperthyroid rats.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Perspectives of Thyroxine Administration in Neonatal Rats

Varma¹,

Crawford²

1979

Horm Res

View full text Add to dashboard Cite

Newborn pups were injected with normal saline (group A) and exogenous thyroxine (group B). Elevated T₄ and decreased TSH levels from day 7 in group B continued until day 35. T₄ and TSH were in normal range by day 42 and were similar to group A. Weight gain was significantly lower in group B. On day 45, half hourly injections (subcutaneous) of TRH were given to half of group A and group B each. Remaining halves were injected with saline. TSH response to TRH was significantly decreased in group B rats. Thus, neonatal hyperthyroidism results in (1) permanent decrease in pituitary reserve of TSH secretion and (2) a permanent imprinting regarding growth and thyroidal development and thus, neonatal period is critical for thyroidal development.

show abstract

“…However, they observed a significant decrease in T3, T4, and TSH serum concentrations and suggested that the HyperPNT causes a permanent dysfunction of the HPT axis in adult rats. Bakke et al (1974) also proposed that hyperthyroidism triggered during the NP leads to hypothyroidism in adult rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of neonatal hyperthyroidism on GH gene expression reprogramming and physiological repercussions in rat adulthood

Souza¹,

Silva²,

Nunes³

2006

Journal of Endocrinology

View full text Add to dashboard Cite

The neonatal period (NP) is a critical phase of the development in which the expression pattern of most genes is established. Thyroid hormones (TH) play a key role in this process and, alterations in its availability in the NP may lead to different patterns of gene expression, which might reflect in the permanent expression of several genes in the adulthood. GH gene expression in the pituitary is greatly dependent on TH in the early postnatal life; thus, modifications of thyroid state in NP might lead to alterations in GH gene expression as well as to physiological repercussions in the adult life. This study aimed to investigate this possibility by means of the induction of a neonatal hyperthyroidism in rats (4 mg of 3,5,30 -triiodo-L-thyronine (T3)/100 g body weight, s.c.) for 5, 15 or 30 days, and further evaluation of GH gene expression, as well as its physiological consequences in adult rats subjected to a transient hyperthyroidism in the first 30 days of life. GH mRNA level was shown to be increased in T3-treated rats for 5 days; when the treatment was extended to 15 or 30 days, the GH mRNA levels were similar to the control group. Moreover, rats treated with T3 for 30 days and killed when 90 days old, i.e., 60 days at the end of the T3 treatment, showed decreased GH mRNA content, body weight, bone mineral density, and lean body mass. In conclusion: (1) T3 effects on GH gene expression depend on the period of life in which the hyperthyroidism is set and on the length of T3 treatment in the NP and (2) transient neonatal hyperthyroidism leads to a lower GH mRNA expression in adult life accompanied by physiological repercussions indicative of GH deficiency.

show abstract

The Late Effects of Neonatal Hyperthyroidism upon the Hypothalamic-Pituitary-Thyroid Axis in the Rat

Cited by 43 publications

References 4 publications

Type 3 deiodinase is critical for the maturation and function of the thyroid axis

Type 3 deiodinase is critical for the maturation and function of the thyroid axis

Long-Term Perspectives of Thyroxine Administration in Neonatal Rats

Effect of neonatal hyperthyroidism on GH gene expression reprogramming and physiological repercussions in rat adulthood

Contact Info

Product

Resources

About