DOPAMINERGIC REGULATION OF PITUITARY-FUNCTION IN THE LATE-GESTATION FETAL SHEEP

Development of the fetal ovine pituitary is essential for normal matur ation and initiation of the parturition process, as well as for orches trating endocrine responses to stress in utero. Increases in the biosy nthesis of ACTH and prolactin (PRL) occur in the late-gestation fetal sheep pituitary. In the anterior lobe (AL) of the pituitary, pro-opiom elanocortin (POMC) biosynthesis and processing are primarily regulated by corticotrophin-releasing hormone and vasopressin. However, POMC in the intermediate lobe (IL) and PRL in the AL are known to be primaril y regulated by dopamine, via the D-2 receptor, in adult sheep. Because of the importance of ACTH and PRL during gestation we have investigat ed a potential role of dopamine in the control of both IL melanotrophs and AL lactotrophs and corticotrophs, in late gestation. Catheters we re implanted into a maternal femoral artery and vein, fetal carotid ar tery and jugular vein as well as into the amniotic cavity At day 130 o f gestation, fetuses were infused intravenously with either the specif ic D-2 receptor agonist bromocriptine (n = 5) or vehicle (n = 5), for 5 days. Blood samples were taken throughout the experiment and pituita ries were removed at the end of the treatment period. Bromocriptine ca used a significant decrease (>50%) in POMC mRNA levels in the IL. In c ontrast,bromocriptine had no significant effect on POMC mRNA levels or distribution in the AL. Fetal arterial ACTH and cortisol concentratio ns were unaffected by the bromocriptine infusion, compared with vehicl e-infused controls. There was a dramatic decrease (>80%) in plasma PRL concentrations, compared with the control fetuses. However, PRL mRNA levels in the AL were not significantly affected by bromocriptine. In conclusion, we have found that bromocriptine inhibits aspects of both melanotroph and lactotroph function in late-gestation fetal sheep. The data indicate that the fetal pituitary possesses functional D-2 recep tors in late gestation.