Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women.
BACKGROUND
The ACTH-cortisol axis in women is activated and associated with decreased ACTH potency, estimated by relating ACTH and cortisol pulse masses. Recently, a new accurate method for constructing the endogenous dose-response relationship was introduced, which is based on the relation between ACTH concentrations and associated cortisol secretion rates within cortisol bursts.


OBJECTIVE
The endogenous dose-response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness.


METHODS
Twenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h.


RESULTS
ACTH and cortisol secretion rates, analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were quantified.


RESULTS
The initial potency (negative logarithm) was -7.83 ± 0.75 (mean ± s.e.m.) in obese women and -10.14 ± 1.08 in lean women (P=0.10), and the corresponding values for the recovery phase were -26.62 ± 2.21 and -36.67 ± 1.66 (P=0.004). The sensitivity (curve slope) amounted to 0.468 ± 0.05 in obese women and 0.784 ± 0.09 in normal weight women (P=0.004). The efficacy (maximal value) was 17.6 ± 4.9 nmol/l per min in obese women and 26.3 ± 3.8 nmol/l per min in normal weight women (P=0.009). Basal secretion rate, inflection point, and EC(50) values were not different. Bromocriptine or acipimox did not change the dose-response curve.


CONCLUSIONS
The ACTH-cortisol relation in obesity in women is characterized by decreased sensitivity and efficacy, thus explaining non-elevated serum cortisol concentrations despite increased plasma ACTH levels.
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, The Netherlands. f.roelfsema@lumc.nl
Ferdinand
F
Roelfsema
Hanno
H
Pijl
Daniel M
DM
Keenan
Johannes D
JD
Veldhuis
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000378:metabolism; D008962:Models, Theoretical; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism
D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone