Hyperadrenocorticism and food restriction-induced life extension in the rat: evidence for divergent regulation of pituitary proopiomelanocortin RNA and adrenocorticotropic hormone biosynthesis.
Level 5 - mechanism / opinion, no new human data
Animal physiology laboratory experiment without human subjects (Oxford CEBM Level 5).
PubMed 7545529 · doi:10.1093/gerona/50a.5.b288
What was done
The authors evaluated 3-month-old male Fischer 344 rats fed either ad libitum (AL) or a food-restricted (FR) diet (60% of AL calories) starting at 6 weeks of age. They measured morning (AM) and evening (PM) levels of plasma corticosterone, plasma adrenocorticotropic hormone (ACTH), and anterior pituitary contents of ACTH, proopiomelanocortin (POMC) mRNA, POMC primary transcript, and processing intermediates.
What was found
Plasma corticosterone was 2-fold higher in FR rats in PM samples compared to AL rats, with no difference in AM samples. Plasma ACTH did not differ in PM samples but was 20% lower in FR rats in AM samples (p < .05). Anterior pituitary ACTH content was 50% lower in FR rats in both AM and PM samples (p < .01). Pituitary POMC mRNA, primary transcript, and processing intermediates were not decreased in FR rats, and PM POMC primary transcript was significantly elevated in FR rats (p < .05).
Why it matters
The findings show that food restriction-induced elevations in corticosterone occur alongside suppressed pituitary ACTH stores rather than increased ACTH production, indicating divergent regulation of POMC transcription and ACTH biosynthesis.
Limits
The abstract does not state the sample size (n). The experiment was limited to young male Fischer 344 rats, precluding direct generalizability to females, aging animals, or humans. Downstream mechanisms driving hyperadrenocorticism despite reduced pituitary ACTH were not fully resolved.
Cited by
- supports Animals placed on calorie restriction or intermittent fasting have elevated cortisol/corticosterone levels despite living longer.