DIRECT STIMULATION OF BOVINE OVARIAN PROGESTERONE SECRETION BY LOW CONCENTRATIONS OF a-INTERFERON

ABSTRACT The ruminant conceptus secretes proteins during early pregnancy which maintain the corpus luteum. These trophoblast proteins are related to the αII-interferons and prevent luteolysis indirectly by disrupting the secretion of endometrial prostaglandin. Although trophoblast interferons appear to be largely confined to the uterine lumen, it remains possible that they also act peripherally. This report describes in vitro studies which suggest that interferon may influence hormone secretion by the ovary directly. The study employed i) a well defined serum-free culture model in which bovine granulosa cells secrete the luteal hormones progesterone and oxytocin, and ii) serum-free and serum-supplemented cultures of cells from early CL. Dose-response experiments were performed using bovine recombinant α-interferon (brIFN). Progesterone and oxytocin secretions were measured over 4-5 days of culture and DNA content was also determined. Low concentrations of brIFN (10−15 mol/l to 10−11 mol/l) stimulated progesterone secretion by granulosa cells by up to three fold, without significantly affecting oxytocin concentrations or culture DNA content. Concentrations of 10−10 mol/l to 10−7 mol/l suppressed progesterone secretion in a log dose-related manner (r=0.97) with evidence of toxicity (lower oxytocin concentrations and significantly reduced DNA compared with controls). Progesterone secretion by luteal cells in serum-free culture was stimulated in the presence of 10−15 mol/l brIFN, whilst high concentrations again caused inhibition. The data show that ovarian cells can respond directly to low concentrations of interferon-like proteins. They also demonstrate an inhibition by high doses which may mask the stimulatory effect in this model. The data suggest that the early corpus luteum may be directly influenced by α-interferon. A stimulation of progesterone, but not of oxytocin, secretion from ovarian cells would be consistent with a role for conceptus proteins in maintaining the corpus luteum of pregnancy.