The effect of acute immuno-neutralisation of inhibin in ewes during the early luteal phase of the oestrous cycle on ovarian hormone secretion and follicular development.

Abstract

Ewes with ovarian autotransplants received either inhibin antiserum (10 ml i.v. raised in sheep against recombinant 32 kDa human inhibin; n = 6) or sheep serum (10 ml i.v.; n = 5) on day 3 of the luteal phase with additional daily injections (1 ml i.v.) from 48 h after the initial bolus until day 13. Jugular and ovarian venous blood samples were taken 4-hourly over days 2-13 of the luteal phase. Blood samples were also taken at more frequent intervals (every 10-15 min for 2-3 h) to examine pulsatile secretory responses from the ovary to endogenous and gonadotrophin-releasing hormone-induced (150 ng i.m.) LH pulses on days 4, 6, 8, 10 and 12 of the luteal phase. Plasma FSH levels, ovarian steroid secretion and ovarian follicular development were measured. The ovarian follicle population was estimated daily by real time ultrasound scanning. Immunisation against inhibin resulted in a 3- to 4-fold increase (P < 0.001) in plasma FSH levels within 8 h with levels remaining elevated over controls for 6-7 days. Within 24 h of immunisation there was an increase in the number of small ovarian follicles (P < 0.05) and by 3 days after treatment immunised ewes had 4-6 large ovarian follicles/ewe with this increase in the total number of large follicles being maintained for the rest of the experimental period (P < 0.05). Mean ovarian oestradiol secretion during intensive bleeds was not different from controls 24 h after immunisation, but by 3 days after immunisation it was elevated 4- to 5-fold (P < 0.001) over controls with this increase being maintained throughout the experiment. Similar responses to immunisation against inhibin in androstenedione secretion were observed although mean androstenedione secretion was not elevated until 7 days after treatment. In vitro antibody titres in immunised ewes remained elevated but declined steadily (P < 0.001) over the experimental period. We conclude that the initial stimulation of follicle development and ovarian steroid secretion following passive immunisation against inhibin can be attributed to increased blood FSH. However, the fact that with time FSH declined but increased follicle development was sustained, despite maintenance of high circulating antibody titres, suggests that on a longer term basis inhibin immunisation may stimulate ovarian function by interfering with the modulation of follicle development by inhibin at an ovarian level.