EVIDENCE FOR STEROID CONTROL OF A PUTATIVE ANGIOGENIC FACTOR IN THE PORCINE UTERUS

The formation of new capillaries, both in extraembryonic membranes and in the maternal endometrium, is an essential prerequisite for appropriate feto-maternal relationships throughout pregnancy. At present there is no indication of the nature of the uterine angiogenic stimulus. In-vitro, degradation products of hyaluronic acid, following its catalysis by hyaluronidase, have been shown to have angiogenic properties. In the current study, levels of hyaluronic acid in endometrial tissue and of hyaluronidase and hyaluronic acid in uterine flushings were measured during the oestrous cycle and early pregnancy. The concentration of both hyaluronic acid and hyaluronidase in uterine flushings followed the growth and regression of the corpus luteum, in that basal levels detected on days 0 and 6 increased to peak concentrations on days 12 and 15. By day 18, levels of both hyaluronidase and hyaluronic acid had decreased in cyclic gilts, but remained increased in pregnant pigs. Tissue concentrations of hyaluronic acid were not affected by pregnancy or by the day of the oestrous cycle. In a subsequent experiment, four groups of gilts were ovariectomized on day 4 and thereafter received daily injections of corn oil, progesterone, oestrogen or a combination of oestrogen and progesterone. Hyaluronidase was undetectable in uterine flushings collected on day 15 from corn oil- and oestrogen-treated gilts, but present in similar amounts in uterine flushings from gilts treated with progesterone and progesterone plus oestrogen. Similarly, uterine fluid concentrations of hyaluronic acid were increased in progesterone- and progesterone plus oestrogen-treated gilts, but not in corn oil- or oestogen-treated pigs. Tissue concentrations of hyaluronic acid were unaffected by steroid treatment. These results indicate that progesterone stimulates secretion of hyaluronidase and hyaluronic acid; both substances believed to be associated with the presence of an angiogenic factor in the pig uterus, but there was no evidence of a synergistic interaction between progesterone and estrogen.