CHANGES IN THE SENSITIVITY OF THE PITUITARY GLAND TO LUTEINIZING HORMONE RELEASING FACTOR DURING THE OESTROUS CYCLE OF THE RAT

SUMMARY The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested at various times of the oestrous cycle of the rat in order to assess the relative importance of changes in pituitary sensitivity in the timing and magnitude of the preovulatory surge of luteinizing and follicle-stimulating hormones (LH and FSH). The minimal dosage of LH-RF which consistently induced ovulation in rats anaesthetized with sodium pentobarbitone (Nembutal) immediately before the critical period of pro-oestrus was 50 ng/100 g body weight, and this was used as the standard dose throughout the study. The LH-RF was injected either intravenously into animals anaesthetized with Nembutal 30 min to 1 h before, or into conscious animals through a cardiac catheter which had been inserted several days before. Most experiments were carried out on rats which had exhibited regular 4-day oestrous cycles, although results from animals with 5-day cycles are also presented and discussed. Blood samples were taken immediately before and at frequent intervals after the injection of LH-RF, and the concentrations of LH and FSH in these samples were determined by radioimmunoassay. With respect to the secretion of LH, in both anaesthetized and conscious animals with regular 4-day cycles a tenfold increase in pituitary sensitivity occurred between the early afternoon of dioestrus and pro-oestrus. This was followed by a marked (50-fold) increase which reached a peak at 17.00–18.00 h of pro-oestrus. The phase of marked increase in sensitivity appeared to commence at about the time of the onset of the pre-ovulatory surge of LH and continued for some hours after. Pituitary sensitivity then declined through oestrus and metoestrus, reaching a nadir at 14.00 h of dioestrus. From 15.00 to 22.30 h of pro-oestrus there was a significant positive correlation between the pre-injection levels of and maximal increments in plasma LH, and this, together with the fact that the marked increase in sensitivity could be abolished by administering Nembutal before the critical period, raised the possibility that endogenous LH-RF, presumably secreted in greater amounts during the early afternoon of pro-oestrus, may exert a priming effect on the anterior pituitary gland. Pituitary responsiveness to LH-RF with respect to the secretion of FSH was also at its highest at 17.00–18.00 h of pro-oestrus. However, in contrast to LH, the mean level of FSH before injection reached a peak at 05.00 h of oestrus, 11 h after the maximum FSH response to LH-RF. These results suggest that a change in pituitary sensitivity to LH-RF may play an important role in determining the magnitude of the pre-ovulatory surge of LH, but it would appear that the timing and duration of the surge depend on other factors as well. The relationship between the secretion of LH and ovulation is discussed with respect to the finding that there appeared to be no correlation between the number of ova shed and the maximal levels of plasma LH after injection.