Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women.
OBJECTIVE
In hyperandrogenic women, hyperinsulinaemia amplifies 17 α-hydroxycorticosteroid intermediate response to ACTH, without alterations in serum cortisol or androgen response to stimulation. The aim of the study is to assess whether acute hyperinsulinaemia determines absolute changes in either basal or ACTH-stimulated adrenal steroidogenesis in these subjects.


METHODS
Twelve young hyperandrogenic women were submitted in two separate days to an 8 h hyperinsulinaemic (80  mU/m² × min) euglycaemic clamp, and to an 8 h saline infusion. In the second half of both the protocols, a 4 h ACTH infusion (62.5  μg/h) was carried out. Serum cortisol, progesterone, 17 α-hydroxyprogesterone (17-OHP), 17 α-hydroxypregnenolone (17-OHPREG), DHEA and androstenedione were measured at basal level and during the protocols. Absolute adrenal hormone secretion was quantified by measuring C19 and C21 steroid metabolites in urine collected after the first 4 h of insulin or saline infusion, and subsequently after 4 h of concurrent ACTH infusion.


RESULTS
During insulin infusion, ACTH-stimulated 17-OHPREG and 17-OHP were significantly higher than during saline infusion. No significant differences in cortisol and androgens response to ACTH were found between the protocols. Nevertheless, urinary excretion of ACTH-stimulated C19 and C21 steroid metabolites was significantly higher during hyperinsulinaemia than at basal insulin levels (both P < 0.005). Changes in steroid metabolites molar ratios suggested stimulation by insulin of 5 α-reductase activity.


CONCLUSIONS
These in vivo data support the hypothesis that insulin acutely enhances ACTH effects on both the androgen and glucocorticoid pathways.
Division of Endocrinology and Metabolism Clinical Chemistry Laboratory, University and Azienda Integrata Ospedaliera Universitaria di Verona, P.le Stefani 1, 37126 Verona, Italy.
Flavia
F
Tosi
Carlo
C
Negri
Elisabetta
E
Brun
Roberto
R
Castello
Giovanni
G
Faccini
Enzo
E
Bonora
Michele
M
Muggeo
Vincenzo
V
Toscano
Paolo
P
Moghetti
D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D000728:Androgens / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D017588:Hyperandrogenism / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D015592:Immunoradiometric Assay; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood
D000728:Androgens; D005938:Glucocorticoids; D007328:Insulin; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone