Possible mechanisms for reduction of circulating concentrations of progesterone by interferon-alpha in cows: effects on hyperthermia, luteal cells, metabolism of progesterone and secretion of LH.
Experiments were performed to determine the mechanism by which recombinant bovine interferon-alpha I1 (rbIFN-alpha) causes an acute reduction in plasma concentrations of progesterone. In experiment 1, administration of a prostaglandin synthesis inhibitor blocked rbIFN-alpha-induced hyperthermia but did not prevent the decline in plasma concentrations of progesterone. The decline in progesterone concentrations caused by rbIFN-alpha was, therefore, not a direct consequence of the associated hyperthermia or of pathways mediated through prostaglandin synthesis. It is also unlikely that rbIFN-alpha acts to increase the clearance of progesterone since injection of rbIFN-alpha did not decrease plasma concentrations of progesterone in ovariectomized cows given an intravaginal implant of progesterone (experiment 2). In experiment 3, rbIFN-alpha did not affect basal and LH-induced release of progesterone from cultured luteal slices, indicating that rbIFN-alpha is unlikely to affect luteal function directly. Injection of rbIFN-alpha did, however, cause a decrease in plasma concentrations of LH in ovariectomized cows (experiment 4) that coincided temporally with the decrease in progesterone concentrations seen in cows having a functional corpus luteum. The present results strongly suggest that rbIFN-alpha acts to reduce secretion of progesterone by interfering with pituitary support for luteal synthesis of progesterone. The finding that rbIFN-alpha can inhibit LH secretion implies that interferon-alpha molecules should be considered among the cytokines that can regulate hypothalamic or pituitary function.
Barros
C M
CM
Departamento de Farmacologia, Universidade Estadual Paulista, Botucatu, Brazil.
Betts
J G
JG
Thatcher
W W
WW
Hansen
P J
PJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002417:Cattle / Q000502:physiology*; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D008184:Luteal Cells / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000378:metabolism / Q000502:physiology; D011374:Progesterone / Q000097:blood* / Q000378:metabolism; D011994:Recombinant Proteins
D007370:Interferon Type I; D011994:Recombinant Proteins; D011374:Progesterone; D007986:Luteinizing Hormone