Dopaminergic regulation of pituitary function in the late-gestation fetal sheep.
Development of the fetal ovine pituitary is essential for normal maturation and initiation of the parturition process, as well as for orchestrating endocrine responses to stress in utero. Increases in the biosynthesis of ACTH and prolactin (PRL) occur in the late-gestation fetal sheep pituitary. In the anterior lobe (AL) of the pituitary, pro-opiomelanocortin (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 primarily regulated by dopamine, via the D2 receptor, in adult sheep. Because of the importance of ACTH and PRL during gestation we have investigated a potential role of dopamine in the control of both IL melanotrophs and AL lactotrophs and corticotrophs, in late gestation. Catheters were implanted into a maternal femoral artery and vein, fetal carotid artery and jugular vein as well as into the amniotic cavity. At day 130 of gestation, fetuses were infused intravenously with either the specific D2 receptor agonist bromocriptine (n = 5) or vehicle (n = 5), for 5 days. Blood samples were taken throughout the experiment and pituitaries were removed at the end of the treatment period. Bromocriptine caused a significant decrease (> 50%) in POMC mRNA levels in the IL. In contrast, bromocriptine had no significant effect on POMC mRNA levels or distribution in the AL. Fetal arterial ACTH and cortisol concentrations were unaffected by the bromocriptine infusion, compared with vehicle-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 D2 receptors in late gestation.
Matthews
S G
SG
Department of Physiology, University of Toronto, Ontario, Canada.
Fraser
M
M
Challis
J R
JR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D017403:In Situ Hybridization; D010902:Pituitary Gland / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D011388:Prolactin / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012756:Sheep / Q000196:embryology* / Q000378:metabolism
D018491:Dopamine Agonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D004298:Dopamine; D006854:Hydrocortisone