Central hypothyroidism is associated with advanced age in male fischer 344/N rats: In vivo and in vitro studies

Giovanni Cizza; Linda S. Brady; Aldo E. Calogeroj; Gyorgy Bagdy; Allyson B. Lynn; Mitchel A. Kling; Marc R. Blackman; George P. Chrousos; Philip W. Gold

doi:10.1210/endo.131.6.1446609

Central hypothyroidism is associated with advanced age in male fischer 344/N rats: In vivo and in vitro studies

Giovanni Cizza, Linda S. Brady, Aldo E. Calogeroj, Gyorgy Bagdy, Allyson B. Lynn, Mitchel A. Kling, Marc R. Blackman, George P. Chrousos, Philip W. Gold

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Abstract

We investigated age-related alterations in hypothalamic-pituitary-thyroid function in a series of in vivo and in vitro studies in 2-, 8-, 18-, and 24-month-old male Fischer 344/N (F344/N) rats. Thyroid histology showed progressive follicular loss with advancing age; this was associated with significant and progressive decrements in plasma levels of free T₄ and free T₃, but not immunoreactive TSH, which remained unchanged with age. This was accompanied by a progressive age-dependent loss in in vivo responsivity of the thyrotroph to synthetic TRH and a paradoxically augmented response of GH to this peptide in the oldest rats. Steady state levels of prepro-TRH mRNA in the hypothalamic paraventricular nucleus were decreased with age, whereas TRH content in and in vitro secretion by whole hypothalami remained unchanged. Both anterior pituitary steady state TSH β-subunit mRNA levels and TSH content were decreased with age. Taken together, these data suggest that aging in male F344/N rats is associated with a progressive, centrally mediated decrease in thyroid function. The relative contributions to this phenomenon of age-related alterations in suprahypothalamic and/or hypothalamic vs. pituitary thyrotropic function remain to be determined, as do the relationships between changes in hypothalamic-pituitary-thyroid function and those in aging per se.

Original language	English (US)
Pages (from-to)	2672-2680
Number of pages	9
Journal	Endocrinology
Volume	131
Issue number	6
DOIs	https://doi.org/10.1210/endo.131.6.1446609
State	Published - Dec 1992
Externally published	Yes

ASJC Scopus subject areas

Endocrinology

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@article{4803d06eabf44b30be90572337114bcb,

title = "Central hypothyroidism is associated with advanced age in male fischer 344/N rats: In vivo and in vitro studies",

abstract = "We investigated age-related alterations in hypothalamic-pituitary-thyroid function in a series of in vivo and in vitro studies in 2-, 8-, 18-, and 24-month-old male Fischer 344/N (F344/N) rats. Thyroid histology showed progressive follicular loss with advancing age; this was associated with significant and progressive decrements in plasma levels of free T4 and free T3, but not immunoreactive TSH, which remained unchanged with age. This was accompanied by a progressive age-dependent loss in in vivo responsivity of the thyrotroph to synthetic TRH and a paradoxically augmented response of GH to this peptide in the oldest rats. Steady state levels of prepro-TRH mRNA in the hypothalamic paraventricular nucleus were decreased with age, whereas TRH content in and in vitro secretion by whole hypothalami remained unchanged. Both anterior pituitary steady state TSH β-subunit mRNA levels and TSH content were decreased with age. Taken together, these data suggest that aging in male F344/N rats is associated with a progressive, centrally mediated decrease in thyroid function. The relative contributions to this phenomenon of age-related alterations in suprahypothalamic and/or hypothalamic vs. pituitary thyrotropic function remain to be determined, as do the relationships between changes in hypothalamic-pituitary-thyroid function and those in aging per se.",

author = "Giovanni Cizza and Brady, {Linda S.} and Calogeroj, {Aldo E.} and Gyorgy Bagdy and Lynn, {Allyson B.} and Kling, {Mitchel A.} and Blackman, {Marc R.} and Chrousos, {George P.} and Gold, {Philip W.}",

year = "1992",

month = dec,

doi = "10.1210/endo.131.6.1446609",

language = "English (US)",

volume = "131",

pages = "2672--2680",

journal = "Endocrinology",

issn = "0013-7227",

publisher = "The Endocrine Society",

number = "6",

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TY - JOUR

T1 - Central hypothyroidism is associated with advanced age in male fischer 344/N rats

T2 - In vivo and in vitro studies

AU - Cizza, Giovanni

AU - Brady, Linda S.

AU - Calogeroj, Aldo E.

AU - Bagdy, Gyorgy

AU - Lynn, Allyson B.

AU - Kling, Mitchel A.

AU - Blackman, Marc R.

AU - Chrousos, George P.

AU - Gold, Philip W.

PY - 1992/12

Y1 - 1992/12

N2 - We investigated age-related alterations in hypothalamic-pituitary-thyroid function in a series of in vivo and in vitro studies in 2-, 8-, 18-, and 24-month-old male Fischer 344/N (F344/N) rats. Thyroid histology showed progressive follicular loss with advancing age; this was associated with significant and progressive decrements in plasma levels of free T4 and free T3, but not immunoreactive TSH, which remained unchanged with age. This was accompanied by a progressive age-dependent loss in in vivo responsivity of the thyrotroph to synthetic TRH and a paradoxically augmented response of GH to this peptide in the oldest rats. Steady state levels of prepro-TRH mRNA in the hypothalamic paraventricular nucleus were decreased with age, whereas TRH content in and in vitro secretion by whole hypothalami remained unchanged. Both anterior pituitary steady state TSH β-subunit mRNA levels and TSH content were decreased with age. Taken together, these data suggest that aging in male F344/N rats is associated with a progressive, centrally mediated decrease in thyroid function. The relative contributions to this phenomenon of age-related alterations in suprahypothalamic and/or hypothalamic vs. pituitary thyrotropic function remain to be determined, as do the relationships between changes in hypothalamic-pituitary-thyroid function and those in aging per se.

AB - We investigated age-related alterations in hypothalamic-pituitary-thyroid function in a series of in vivo and in vitro studies in 2-, 8-, 18-, and 24-month-old male Fischer 344/N (F344/N) rats. Thyroid histology showed progressive follicular loss with advancing age; this was associated with significant and progressive decrements in plasma levels of free T4 and free T3, but not immunoreactive TSH, which remained unchanged with age. This was accompanied by a progressive age-dependent loss in in vivo responsivity of the thyrotroph to synthetic TRH and a paradoxically augmented response of GH to this peptide in the oldest rats. Steady state levels of prepro-TRH mRNA in the hypothalamic paraventricular nucleus were decreased with age, whereas TRH content in and in vitro secretion by whole hypothalami remained unchanged. Both anterior pituitary steady state TSH β-subunit mRNA levels and TSH content were decreased with age. Taken together, these data suggest that aging in male F344/N rats is associated with a progressive, centrally mediated decrease in thyroid function. The relative contributions to this phenomenon of age-related alterations in suprahypothalamic and/or hypothalamic vs. pituitary thyrotropic function remain to be determined, as do the relationships between changes in hypothalamic-pituitary-thyroid function and those in aging per se.

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Central hypothyroidism is associated with advanced age in male fischer 344/N rats: In vivo and in vitro studies

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