T. Haak et al., CLINICAL-EVIDENCE FOR A NEUROMODULATOR ACTION OF ENDOTHELIN IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN MAN, EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 105(1), 1997, pp. 46-52
In order to investigate whether the ubiquitous signalling peptide endo
thelin might also act as a neuromodulator in the stimulation of the hy
pothalamic-pituitary-adrenal axis, 15 patients (4 female, 11 male, age
d 35-67 years) with hypopituitarism were investigated and the results
were compared to those of 8 healthy male volunteers (aged 24-31 years)
. Patients and controls received double-blind in random order either 0
.1 IE per kg body weight regular insulin (insulin induced hypoglycemia
) or 1 ml 0.9% sodium chloride placebo) on 2 separate days. Control su
bjects only received on an additional day 0.1 IE per kg body weight re
gular insulin plus glucose 10% (euglycemic hyperinsulinemic glucose cl
amp). In control subjects hypoglycemia resulted in a significant incre
ase in adrenocorticotropin (ACTH) and cortisol which was preceded by a
n increase in circulating endothelin levels (p < 0.01 vs placebo and e
uglycemic clamp) while endothelin, ACTH and cortisol remained unchange
d both after placebo and in the euglycemic hyperinsulinemic clamp. In
contrast, patients with hypopituitarism showed neither changes in circ
ulating endothelin levels nor a stimulation of the hypothalamic-pituit
ary-adrenal axis during insulin-induced hypoglycemia. These data demon
strate that 1) endothelin levels are enhanced by metabolic stress 2) t
he responsiveness of endothelin levels to metabolic stress is linked t
o the presence of an intact pituitary gland and 3) endothelin might be
involved in the stimulation of the hypothalamic-pituitary-adrenal axi
s.