Effect of pregnancy and exogenous interferon on synchronous pulsatile release of oxytocin and luteolytic prostaglandin F2  in red deer (Cervus elaphus)

Abstract

Three experiments were carried out to investigate the secretion of luteolytic hormones in red deer hinds during the oestrous cycle, early pregnancy and after administration of interferon, the putative pregnancy recognition signal. Three groups of hinds (n = 8-9 per group) were treated with progesterone-impregnated intravaginal controlled internal drug releasing (CIDR) devices for 13 days (device withdrawal = day 0). Group 1 (n = 9) served as controls; Group 2 (n = 8) received injections of 4 mg recombinant bovine interferon-alpha 1 l twice a day on days 13-18; Group 3 (n = 9) were run with a fertile stag on days 0-3. Plasma samples collected each day on days 16-23 were analysed for progesterone. Plasma samples collected each hour for 16 h on days 4, 10, 16, 18 were analysed for oxytocin and the prostaglandin F2 alpha (PGF2 alpha) metabolite (PGFM). Plasma progesterone concentrations declined to < 1 ng ml-1 between days 18 and 25 in control hinds indicating that luteolysis had occurred, whereas there was no endocrine evidence of luteolysis in interferon-treated or pregnant hinds. Control hinds (6/9) exhibited synchronous pulses of oxytocin and PGF2 alpha secretion on day 18, a greater proportion than on any other day in these hinds or on any day in the interferon-treated or mated hinds (P < 0.05). In a second experiment, close synchrony in secretion of oxytocin and PGF2 alpha pulses was evident in an unmated hind when samples were collected every 12 min on day 18. In a third experiment, oxytocin-induced PGF2 alpha secretion was potentiated by oxytocin administration at an interval of 1 h and inhibited by administration at a 6 h interval (P < 0.05). These results suggest that synchronous pulsatile secretion of oxytocin and PGF2 alpha induces luteolysis and is suppressed by pregnancy or administration of interferon. Oxytocin-induced alterations in uterine oxytocin sensitivity may underlie the pulsatile nature of luteolytic hormone secretion in red deer.

Targeted cancer treatment and fertility: effect of immunotherapy and small molecule inhibitors on female reproduction

“…With prolonged use, however, these agents are associated with development of autoimmunity and resultant hypothyroidism [ (Vitale et al, 2009)]. Study in red deer suggests INF-α suppresses the synchronous pulsatile secretion of oxytocin and prostaglandin F2 alpha (PGF2) from the pituitary gland, and thereby delays or inhibits luteal phase lysis [ (Bainbridge & Jabbour, 1997)]. If validated in humans, this could theoretically improve fertility outcomes in the subset of women with a short luteal phase at baseline.…”