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 production by cultured follicular cells but evidence of an effect of TGF alpha on ovarian hormone secretion in vivo is still required. Eleven ewes with an autotransplanted ovary received, by ovarian arterial infusion, either 5 micrograms/h recombinant rat TGF alpha (n = 6) or placebo (n = 5) for 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 injection of gonadotrophin-releasing hormone (GnRH; 150 ng i.v.). Two hours after the end of the infusion luteal regression was induced with prostaglandin F2 alpha (PGF2 alpha; 125 micrograms i.m.). Ovarian and jugular venous blood samples were taken at 10-min, 15-min or 4-h intervals from 2 h before the start of the infusion until 96 h after PGF2 alpha and the rates of secretion of ovarian oestradiol, inhibin, progesterone and androstenedione were determined. Jugular venous concentrations of LH and FSH were also measured and follicle populations monitored by real-time ultrasound scanning. Infusion of TGF alpha resulted in a significant (P < 0.05) depression in the amplitude of the pulsatile response of oestradiol and androstenedione secretion to the GnRH-induced LH pulse at the end of the infusion. Ovarian inhibin secretion was acutely suppressed by TGF alpha infusion (P < 0.001) and remained lower than controls for the period of the experiment. Luteal phase progesterone secretion was also acutely inhibited (P < 0.001) by infusion of TGF alpha, and in one treated ewe progesterone secretion was elevated 48-84 h after PGF2 alpha. Jugular venous concentrations of FSH in TGF alpha-treated ewes were significantly (P < 0.001) elevated over controls during the first 48 h of the follicular phase and the LH surge was delayed 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 with high follicular phase progesterone, had unusually large (8.7 and 10 mm) follicles present from 48-96 h after PGF2 alpha. We conclude that direct arterial infusion of TGF alpha results in acute inhibition of ovarian steroid and inhibin secretion that is associated with induction of atresia in the population of large follicles. The lack of feedback of ovarian hormones results in a rebound increase of FSH which stimulates the growth of more ovarian follicles and the eventual re-establishment of ovarian hormone secretion and normal cyclicity.