CHANGES IN CIRCULATING AND OVARIAN CONCENTRATIONS OF BIOACTIVE TUMOR-NECROSIS-FACTOR-ALPHA DURING THE FIRST OVULATION AT PUBERTY IN RATS AND IN GONADOTROPIN-HEATED IMMATURE RATS

Tumour necrosis factor alpha (TNF-alpha) concentrations were measured during periods of controlled and natural follicular development and ov ulation in rat ovaries. Concentrations of bioactive TNF-alpha were det ermined in the ovaries and sera of rats during puberty (the period of vaginal opening and the first ovulation) and in immature rats after go nadotrophin treatment. Ovaries and sera were collected from 33-, 35-, 37-, 39-, 41- and 43-day-old rats (n = 6 or 7 per group); vaginal open ing occurs on day 35. The presence of ovarian follicles and corpora lu tea or ova in the oviducts was assessed. For gonadotrophin treatment, a single subcutaneous injection of 5 iu equine chorionic gonadotrophin (eCG) was administered at 08:00h to 28-day-old rats to stimulate foll icular development. A single subcutaneous injection of 10 iu human cho rionic gonadotrophin (hCG) was administered 48 h later to induce ovula tion. Ovaries and sera from three to six animals per group were collec ted 0, 3, 24, 48, 51, 54, 57, 60 and 72 h after injection of eCG. At p uberty, ovarian concentrations of TNF-alpha were highest (approximatel y 1.1 fg mu g(-1) ovarian protein) before vaginal opening and the firs t ovulation. After vaginal opening and ovulation at day 37, ovarian co ncentrations of TNF-alpha were markedly reduced (0.091 fg mu g(-1) ova rian protein) and remained low up to day 43. Serum concentrations of T NF-alpha remained low throughout the period of vaginal opening and the first ovulation (8-32 pg ml(-1)). In 43-day-old rats serum concentrat ions of TNF-alpha increased (105 pg ml(-1)). In the immature ovaries o f 28-day-old rats TNF-alpha concentrations were highest before injecti on of eCG (approximately 1.2 fg mu g(-1) ovarian protein) and decrease d to approximately 0.4 fg mu g(-1) protein 3 h after injection. TNF-al pha concentrations decreased further 24 h after eCG injection ( < 0.1 fg mu g(-1) protein) and remained low until 48 h after eCG injection. Serum concentrations of TNF-alpha did not change during the 48 h perio d after injection of eCG. hCG was administered 48 h after eCG, and ova rian and serum TNF-alpha concentrations increased transiently. Serum T NF-alpha concentrations increased 3 h after hCG and remained elevated until 9 h after injection, after which concentrations decreased. Ovari an concentrations of TNF-alpha increased 6 h after hCG, peaked (approx imately 0.5 fg mu g(-1) protein), and then declined. These results ind icate that during puberty and the first ovulation, circulating and ova rian TNF-alpha concentrations change. In addition, exogenous gonadotro phins alter circulating and ovarian TNF-alpha concentrations. These da ta suggest that TNF-alpha has a role in follicular development and ovu lation during puberty and in immature rats treated with gonadotrophins to induce ovulation.