Influence of Ovarian Steroids on Pituitary Sensitivity to Luteinizing Hormone-Releasing Hormone in the Ovariectomized Guinea Pig*

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Abstract
To determine the sites of positive feedback action of estrogen and progesterone (P), pituitary responsiveness to LHRH under estradiol benzoate (EB) and P influence was examined in the ovariectomized guinea pig. Two to 3 days before the experiment, animals received an implantation of an indwelling venous catheter for blood sampling (drawn every 15 min) and for LHRH administration. Plasma LH was measured by RIA. In the fust experiment, a single dose of LHRH (1.0μg) was given to five groups of animals: non-EB-treated; 12 h, 30 h, and 36 h after 1.5 μg EB; and 30 h after 1.5 μg EB plus 2 h after 0.5 μg P. Plasma LH levels were significantly elevated 15 min after LHRH injection in all treatments. In the subsequent 60-90 min, LH levels decreased exponentially. The peak value was highest in the group of non-EB-treated animals and diminished as time elapsed after EB treatment. P plus EB priming did not facilitate an LH response significantly greater than priming with EB alone. In the second experiment, LHRH was given in a pulsatile fashion at a frequency of one bolus per h for 3 h (0.5 μg/bolus)to five groups of animals: non-EB treated; 12 h, 36 h, and 48 h after 1.5 μg EB; and 36 h after 1.5 μg EB plus 2 h after 0.5 mg P. The response to the first bolus of 0.5 μg LHRH was half of the response to 1.0 μg LHRH observed in the first experiment. Without EB treatment, all three boluses induced LH responses of equal magnitude. On the other hand, LH responses to the second and third boluses of LHRH were highly augmented under estrogen influences, especially 36 and 48 h after EB, indicating the priming effect of LHRH. P plus EB priming did not enhance pituitary responsiveness to the second and third boluses of LHRH more than did EB priming alone after 36 or 48 h. In light of our previous finding that an injection of P is effective in inducing an LH surge within 6-12 h in animals treated with 1.5 μg EB and that barbiturates block the P-induced LH surge, the present experiment suggests that the positive feedback action of P requires activation of the brain rather than the pituitary in order to facilitate the release of LH. In contrast, EB may act on the anterior pituitary as well as on the brain; the priming effect with pulsatile LHRH at the pituitary appears to contribute greatly to the positive feedback action of estrogen. (Endocrinology106: 425, 1980)