ENDOTHELIN STIMULATES ACTH-SECRETION IN THE OVINE FETUS

The endothelins are a series of peptides with potent vasoconstrictor e ffects in vascular tissue; however, they may also have a role as neuro endocrine secretagogues because endothelin and endothelin receptors ha ve been found in hypothalamic and pituitary tissues. Since activation of the fetal hypothalamo-pituitary-adrenal axis is crucial to the proc ess of parturition, the aim of this study was to determine whether end othelin could activate the hypothalamo-pituitary-adrenal axis in the o vine fetus. Catheters were inserted into the carotid artery, jugular v ein and lateral cerebral ventricle of six fetal lambs at 118-122 days' gestation. After a 5-day recovery period, endothelin-3 or placebo (sa line) was infused intravenously (i.v.) or intracerebroventricularly (i .c.v.) over 30-60 min. The dose of endothelin-3 employed was 0.01 and 0.1 mu g min(-1) i.c.v. and 0.1 and 1.0 mu g min(-1) i.v. Arterial blo od was taken from the fetus before, during and for Ih after the infusi on for measurement of ACTH and cortisol. Blood gas analysis was also p erformed. Intravenous endothelin-3 produced a dose-dependent increase in ACTH and cortisol concentrations in fetal plasma and was associated with transient fetal hypoxia and acidosis. pH correlated inversely wi th plasma ACTH (r = -0.701, P < 0.001) and cortisol (r = -0.308, P < 0 .001) concentrations. An increase in ACTH and cortisol concentrations in fetal plasma was also induced by endothelin-3 administered i.c.v. a t 0.1 mu g min(-1) and this was not associated with fetal acidosis The se data suggest that endothelin administered i.v. will stimulate ACTH and cortisol release indirectly through vasoconstriction and acidosis; however, the response to i.c.v. endothelin administration suggests th at it may also act as a central secretagogue for ACTH in the fetus and could therefore play a role in the process of parturition.