Changes in circulating and ovarian concentrations of bioactive tumour necrosis factor alpha during the first ovulation at puberty in rats and in gonadotrophin-treated immature rats.

Tumour necrosis factor alpha (TNF-alpha) concentrations were measured during periods of controlled and natural follicular development and ovulation in rat ovaries. Concentrations of bioactive TNF-alpha were determined in the ovaries and sera of rats during puberty (the period of vaginal opening and the first ovulation) and in immature rats after gonadotrophin treatment. Ovaries and sera were collected from 33-, 35-, 37-, 39-, 41- and 43-day-old rats (n = 6 or 7 per group); vaginal opening occurs on day 35. The presence of ovarian follicles and corpora lutea or ova in the oviducts was assessed. For gonadotrophin treatment, a single subcutaneous injection of 5 iu equine chorionic gonadotrophin (eCG) was administered at 08:00 h to 28-day-old rats to stimulate follicular development. A single subcutaneous injection of 10 iu human chorionic gonadotrophin (hCG) was administered 48 h later to induce ovulation. Ovaries and sera from three to six animals per group were collected 0, 3, 24, 48, 51, 54, 57, 60 and 72 h after injection of eCG. At puberty, ovarian concentrations of TNF-alpha were highest (approximately 1.1 fg micrograms-1 ovarian protein) before vaginal opening and the first ovulation. After vaginal opening and ovulation at day 37, ovarian concentrations of TNF-alpha were markedly reduced (0.091 fg microgram-1 ovarian protein) and remained low up to day 43. Serum concentrations of TNF-alpha remained low throughout the period of vaginal opening and the first ovulation (8-32 pg ml-1). In 43-day-old rats serum concentrations of TNF-alpha increased (105 pg ml-1). In the immature ovaries of 28-day-old rats TNF-alpha concentrations were highest before injection of eCG (approximately 1.2 fg micrograms-1 ovarian protein) and decreased to approximately 0.4 fg microgram-1 protein 3 h after injection. TNF-alpha concentrations decreased further 24 h after eCG injection (< 0.1 fg microgram-1 protein) and remained low until 48 h after eCG injection. Serum concentrations of TNF-alpha did not change during the 48 h period after injection of eCG. hCG was administered 48 h after eCG, and ovarian and serum TNF-alpha concentrations increased transiently. Serum TNF-alpha concentrations increased 3 h after hCG and remained elevated until 9 h after injection, after which concentrations decreased. Ovarian concentrations of TNF-alpha increased 6 h after hCG, peaked (approximately 0.5 fg microgram-1 protein), and then declined. These results indicate that during puberty and the first ovulation, circulating and ovarian TNF-alpha concentrations change. In addition, exogenous gonadotrophins alter circulating and ovarian TNF-alpha concentrations. These data suggest that TNF-alpha has a role in follicular development and ovulation during puberty and in immature rats treated with gonadotrophins to induce ovulation.