THE EFFECT OF OVARIAN ARTERIAL INFUSION OF TRANSFORMING GROWTH-FACTOR-ALPHA ON OVARIAN FOLLICLE POPULATIONS AND OVARIAN HORMONE-SECRETION IN EWES WITH AN AUTOTRANSPLANTED OVARY

Transforming growth factor alpha (TGF alpha) inhibits hormone producti on by cultured follicular cells but evidence of an effect of TGF alpha on ovarian hormone secretion in vivo is still required. Eleven ewes w ith an autotransplanted ovary received, by ovarian arterial infusion, either 5 mu g/h recombinant rat TGF alpha (n = 6) or placebo (n = 5) f or 12 h on day 10 of the luteal phase. Two hours before the start and 1 hour before the end of the infusion each ewe received a single injec tion of gonadotrophin-releasing hormone (GnRH; 150 ng i.v.). Two hours after the end of the infusion luteal regression was induced with pros taglandin F-2 alpha (PGF(2 alpha); 125 mu g i.m.). Ovarian and jugular venous blood samples were taken at 10-min, 15-min or 4-h intervals fr om 2 h before the start of the infusion until 96 h after PGF(2 alpha) and the rates of secretion of ovarian oestradiol, inhibin, progesteron e and androstenedione were determined. Jugular venous concentrations o f LH and FSH wire also measured and follicle populations monitored by real-time ultrasound scanning. Infusion of TGF alpha resulted in a sig nificant (P < 0.05) depression in the amplitude of the pulsatile respo nse of oestradiol and androstenedione secretion to the GnRH-induced LH pulse at the end of the infusion. Ovarian inhibin secretion was acute ly suppressed by TGF alpha infusion (P < 0.001) and remained lower tha n controls for the period of the experiment. Luteal phase progesterone secretion was also acutely inhibited (P < 0.001) by infusion of TGF a lpha, and in one treated ewe progesterone secretion was elevated 48-84 h after PGF(2 alpha). Jugular venous concentrations of FSH in TGF alp ha-treated ewes were significantly (P < 0.001) elevated over controls during the first 48 h of the follicular phase and the LH surge was del ayed for about 10 h (P < 0.05). Infusion of TGF alpha caused a marked decline (P < 0.05) in the number of large follicles within 12 h of the end of the infusion. Two of the six treated ewes, including the one w ith high follicular phase progesterone, had unusually large (8.7 and 1 0 mm) follicles present from 48-96 h after PGF(2 alpha). We conclude t hat direct arterial infusion of TGF alpha results in acute inhibition of ovarian steroid and inhibin secretion that is associated with induc tion of atresia in the population of large follicles. The lack of feed back of ovarian hormones results in a rebound increase of FSH which st imulates the growth of more ovarian follicles and the eventual re-esta blishment of ovarian hormone secretion and normal cyclicity.