Acute progesterone and 17 beta-estradiol modulation of luteinizing hormone secretion by pituitaries of cycling rats superfused in vitro.

During the rat estrous cycle there are marked changes in the concentrations of serum 17 beta-estradiol (E2) and progesterone. The objective of the present study was to examine the acute effects of E2 and progesterone on isolated pituitaries obtained at 1230 h at each stage of the 4-day cycle. At time zero, single quartered anterior pituitaries were placed in a chamber and superfused at 0.5 ml/min with medium 199 with or without steroids for 360 min; sequential 10-min effluent samples were collected. LHRH (10 ng/ml) was administered as two successive 10-min pulses at 120 and 240 min. The proestrous and the diestrous-II pituitaries in vitro exhibited the characteristic LHRH self-priming response: an increased LH secretory response to a second pulse of LHRH in both the absence and presence of steroids in the superfusion medium; however, the magnitude of the response to the initial pulse of LHRH was reduced significantly when E2 (50 pg/ml) was present. The presence of progesterone (50 ng/ml) resulted in a marked augmentation of the LH secretory response to the first pulse of LHRH; when both E2 and progesterone were included in the superfusion medium, the stimulatory effect of progesterone was reduced. The progesterone augmentation of LHRH-induced LH secretion was present after 60 min of steroid exposure in vitro but was not demonstrable after only 10 min of exposure. Cycloheximide inhibited the progesterone augmentation and the LHRH self-priming without affecting the LH secretory response to the initial LHRH pulse in the absence of steroid. Progesterone augmentation was not observed on estrus and diestrous-I. The presence of E2 in the medium, however, resulted in a significant decrease in the response to the first pulse of LHRH for pituitaries from either estrus or diestrous-I. These data 1) demonstrate that E2 by itself suppresses LHRH-induced LH secretion by the proestrous pituitary and 2) provide proof for a direct stimulatory action of progesterone, in the absence of E2, on the proestrous pituitary and suggest a positive feedback role for progesterone during the preovulatory LH surge. (Endocrinology 108: 413, 1981)