Dopaminergic regulation of adrenocorticotrophic hormone, alpha-melanocyte-stimulating hormone and cortisol secretion in the ovine fetus

During ovine fetal development there is a progressive maturation of the hypothalamo-pituitary-adrenal axis which culminates in the onset of birth. The role and regulation of the intermediate lobe of the fetal pituitary gland in relation to this maturational process remains controversial. To test the hypothesis that the pars intermedia of the ovine fetal pituitary is under tonic inhibitory dopaminergic control we treated fetal sheep at day 131 of gestation with a 3-day intravenous infusion of one of the following: the dopamine antagonist sulpiride (0.3 mg/0.5 ml/h; n=12), the dopamine agonist bromocriptine (0.03 mg/0.5 ml/h; n=7) or vehicle (0.1 M tartaric acid in saline; n=8) alone. Fetal plasma concentrations of alpha-MSH were significantly (P<0.01) increased by treatment with sulpiride and decreased (P<0.05) by bromocriptine. The increase in alpha-MSH after sulpiride was characterised by an increase in the amplitude of alpha-MSH pulses pvhereas bromocriptine virtually abolished all pulses of alpha-MSH. Immunoreactive ACTH (IR-ACTH) concentrations were significantly (P<0.05) elevated after sulpiride but were unaffected by bromocriptine. There were no changes in the pulsatile characteristics of TR-ACTH secretion. Cortisol concentrations were unchanged by either treatment. We conclude that fetal alpha-MSH and IR-ACTH are secreted in a pulsatile fashion and are tonically inhibited by dopaminergic pathways. The lack of an effect of endogenously raised alpha-MSH on plasma cortisol concentrations provides evidence that this POMC-derived peptide is not responsible for the regulation of cortisol biosynthesis and/or secretion.