Enhanced hypothalamic-pituitary-adrenocortical axis responses to physostigmine in normal aging.
BACKGROUND
The purpose of this study was to determine the effects of normal human aging on the hypothalamic-pituitary-adrenocortical (HPA) axis response to the centrally active cholinesterase inhibitor physostigmine. This drug stimulates the HPA axis at a suprapituitary level by increasing central nervous system (CNS) cholinergic activity.


METHODS
Plasma ACTH, beta-endorphin (beta E) and cortisol responses to a 10-minute infusion of physostigmine (.0125 mg/kg) were compared between groups of 10 normal older subjects (71 +/- 2 years [mean +/- SEM]) and 9 normal young subjects (27 +/- 2 years). Plasma physostigmine concentrations were measured to assess the comparability of the pharmacologic stimulus between groups.


RESULTS
Endocrine responses were substantially greater in older subjects than young subjects for ACTH (p < .01), beta E (p < .01) and cortisol (p < .01). Plasma physostigmine concentrations did not differ between older and young subjects.


CONCLUSIONS
This study demonstrated increased HPA axis responsivity to a CNS cholinergic stimulus in normal human aging.
Peskind
E R
ER
Geriatric Research, Education and Clinical Center, Seattle, Veterans Affairs Medical Center.
Raskind
M A
MA
Wingerson
D
D
Pascualy
M
M
Thal
L J
LJ
Dobie
D J
DJ
Veith
R C
RC
Dorsa
D M
DM
Murray
S
S
Sikkema
C
C
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010830:Physostigmine / Q000097:blood / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D012737:Sex Factors; D014839:Vomiting / Q000139:chemically induced; D001615:beta-Endorphin / Q000097:blood
D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D010830:Physostigmine; D006854:Hydrocortisone