Endocrinology, Vol 131, 2763-2768, Copyright © 1992 by Endocrine Society
Ontogeny of insulin-induced hypoglycemia stimulation of adrenocorticotropin secretion in the rat: role of catecholamines
M Grino and C Oliver
Laboratoire de Neuroendocrinologie Experimentale, INSERM U. 297, Marseille, France.
We previously reported that insulin-induced hypoglycemia (IIH) induces a
large increase in plasma ACTH and corticosterone levels in the developing
rat during the stress hyporesponsive period and that this effect is
mediated, at least partially, by arginine vasopressin (AVP), but not
corticotropin-releasing factor. Nevertheless, ACTH secretion in response to
IIH in rats immunoneutralized against AVP was still stimulated, suggesting
that other regulatory factors participate in the stimulation of ACTH
secretion during IIH. It has been suggested that, in the adult rat, during
profound hypoglycemia, epinephrine may act at the pituitary level through
beta 2-adrenergic receptors to stimulate ACTH secretion. In this report, we
studied the effect of the blockade of beta-adrenergic receptors on the
pituitary-adrenal axis response to IIH. Rats (20 or 8 day old) were
pretreated with saline or 2.5 mg/kg propranolol (a beta-adrenergic
receptors antagonist) and subsequently injected with 3 IU/kg insulin. In
20-day-old rats, insulin injection induced a large increase of plasma ACTH
concentrations that were unaffected by propranolol pretreatment. In
8-day-old rats, the IIH- induced increase of plasma ACTH levels was
significantly reduced by propranolol pretreatment. Pretreatment of
8-day-old rats with 5 mg/kg CGP 20712A (a selective beta 1-adrenergic
receptor antagonist) did not change the plasma ACTH response to insulin
injection, while pretreatment with 2.5 mg/kg ICI 118551 (a selective beta
2-adrenergic receptor antagonist) resulted in a significant decrease of the
IIH- induced stimulation of ACTH secretion. We next studied the effect of
the blockade of circulating AVP and/or beta-adrenergic receptors on the
pituitary response to IIH. Pretreatment of 8-day-old rats with antiserum
anti-AVP or propranolol was followed by a significant reduction of
IIH-induced increase of plasma ACTH concentrations. No additive effect was
found after pretreatment with both antiserum anti- AVP and propranolol,
suggesting that the stimulatory effect of catecholamines during IIH in
8-day-old rats is mediated through a modulation of hypothalamic AVP
secretion.