261. Resistance to GH signalling through stat5 is an early event in PGF2α induced luteolysis in the ewe

Abstract

Recently we have shown that prostaglandin-induced luteolysis in pregnant rats involves resistance to prolactin-receptor signalling through the JAK2/STAT5 pathway.¹ In the present study, we investigate whether PGF2alpha acts similarly to inhibit GH signalling in the ovine corpus luteum. The oestrous cycle of ewes was synchronised using cloprostenol and CIDR-G devices with oestrus detected by testosterone treated wethers with raddles. Twelve days after the first recorded oestrous mark, ewes were given an intramuscular injection of either saline or cloprostenol (125 µg), followed 1 h later with an intravenous injection (jugular vein) of either vehicle or 1.5 mg recombinant bovine GH (rbGH, Monsanto). After a further 15 min ewes were killed by pentobarbitone overdose and the corpus luteum removed. Tyrosine phosphorylation of STAT5 (STAT-P) in the corpus luteum was determined by immunoprecipitation and Western blot (n = 4 ewes/treatment). STAT5-P levels were relatively low in all ewes that were not treated with rbGH. Treatment with rbGH significantly (P < 0.01) increased STAT5-P in the corpus luteum of ewes pretreated with saline, compared to both control groups. However the STAT5-P response to rbGH was significantly (P < 0.01) reduced by the pretreatment with cloprostenol, although the response remained significantly (P < 0.05) higher than both control groups. In summary we have shown that (1) as expected, the GH-receptor signals through STAT5 in the ovine corpus luteum and (2) cloprostenol induces resistance to this GH-receptor signalling pathway.

   (1) Curlewis et al. (2002). Endocrinology 143, 3984–3993.