Male Fischer 344/N rats show a progressive central impairment of the hypothalamic-pituitary-adrenal axis with advancing age

Giovanni Cizza, Aldo E. Calogero, Linda S. Brady, G. Bagdy, Ettore Bergamini, Marc R. Blackman, George P. Chrousos, Philip W. Gold

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Abstract

We investigated the effects of aging on the regulation of hypothalamic- pituitary-adrenal function and hippocampal steroid receptors in a series of in vivo and in vitro studies conducted in healthy intact 2-, 8-, 18-, and 24- month-old male Fischer 344/N rats. Basal plasma ACTH levels were similar among age groups, and basal plasma corticosterone levels showed a significant aging-associated decline. Two iv doses (2 and 20 μg/kg BW) of rat CRF elicited significantly greater and delayed ACTH and greater corticosterone responses in older rats, consistent with the pattern encountered in hypothalamic CRF deficiency. In contrast, the iv injection of a muscarinic agonist, arecoline, elicited similar ACTH and corticosterone responses in all age groups. An iv injection of ACTH-(1-24) evoked lower corticosterone responses in the older (18- and 24-month-old) than in the younger (2- and 8- month-old) groups of rats, consistent with an impairment of hypothalamic- pituitary-adrenal axis function in older animals. Steady state mRNA levels of mineralocorticoid and glucocorticoid receptors were significantly decreased in the hippocampus of the 8-, 18-, and 24-month-old rats, compatible with maturational, rather than senescent, changes. CRF mRNA levels in the paraventricular nucleus of the hypothalamus, CRF content, and in vitro secretion by whole explanted hypothalami were progressively and significantly reduced with age, whereas the steady state levels of arginine vasopressin mRNA were significantly increased with age. Steady state levels of POMC mRNA were decreased, and ACTH content and in vitro secretion by corticotrophs were increased with age in the anterior pituitary. We conclude that male Fischer 344/N rats show a progressive hypothalamic CRH deficiency with advancing age, which appears to be associated with elevated production of arginine vasopressin in the hypothalamus.

Original languageEnglish
Pages (from-to)1611-1620
Number of pages10
JournalEndocrinology
Volume134
Issue number4
DOIs
Publication statusPublished - Apr 1994

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Corticosterone
Adrenocorticotropic Hormone
Hypothalamus
Messenger RNA
Arginine Vasopressin
Age Groups
Arecoline
Corticotrophs
Cosyntropin
Mineralocorticoid Receptors
Muscarinic Agonists
Pro-Opiomelanocortin
Injections
Paraventricular Hypothalamic Nucleus
Steroid Receptors
Glucocorticoid Receptors
Hippocampus
In Vitro Techniques

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Male Fischer 344/N rats show a progressive central impairment of the hypothalamic-pituitary-adrenal axis with advancing age. / Cizza, Giovanni; Calogero, Aldo E.; Brady, Linda S.; Bagdy, G.; Bergamini, Ettore; Blackman, Marc R.; Chrousos, George P.; Gold, Philip W.

In: Endocrinology, Vol. 134, No. 4, 04.1994, p. 1611-1620.

Research output: Contribution to journalArticle

Cizza, G, Calogero, AE, Brady, LS, Bagdy, G, Bergamini, E, Blackman, MR, Chrousos, GP & Gold, PW 1994, 'Male Fischer 344/N rats show a progressive central impairment of the hypothalamic-pituitary-adrenal axis with advancing age', Endocrinology, vol. 134, no. 4, pp. 1611-1620. https://doi.org/10.1210/en.134.4.1611
Cizza, Giovanni ; Calogero, Aldo E. ; Brady, Linda S. ; Bagdy, G. ; Bergamini, Ettore ; Blackman, Marc R. ; Chrousos, George P. ; Gold, Philip W. / Male Fischer 344/N rats show a progressive central impairment of the hypothalamic-pituitary-adrenal axis with advancing age. In: Endocrinology. 1994 ; Vol. 134, No. 4. pp. 1611-1620.
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