Acute and chronic estradiol-17beta inhibition of LH release in prepubertal female pigs: time course and site of action.
It has been demonstrated that 5.0 mug estradiol-17beta (E2) iv inhibits spontaneous episodic release (SER) of LH from 3-9 h after injection in immature female pigs (gilts). To understand this phenomenon we tested pituitary response (PR) to synthetic LH-RH/FSH-RH (LH-RH) for 13 h after identical E2 treatment in eight 7-8-week-old gilts. Using chronic cannulae PR was determined by measuring the change in plasma LH (delta LH) by RIA after iv injection of 2.0 mug LH-RH. PR was determined every 2 h starting 1 or 2 h before E2 or saline treatments. The PR prior to treatment was 4.3 plus or minus 0.3 ng/ml. By the second releasing-hormone challenge PR in controls was depressed, remaining at about 2.5 ng/ml thereafter. Compared with controls PR depression was greater (P less than 0.005) 1 h following E2 (delta LH = 1.0 plus or minus 0.4 ng/ml). Responsiveness then returned toward pretreatment levels and from 6 h post-treatment onward PR was not different from controls. Initial inhibition of SER may therefore be located in the pituitary and brain. However, after 4 h inhibition appears to be purely neural. Earlier studies showed that subcutaneous (SC) implants of E2 for 3 days in prepubertal gilts depressed PR to LH-RH. We further examined the effect upon PR of implants releasing physiologic levels of E2. PR was evaluated as above at 2-h intervals for 12 h after SC implantation of silastic capsules containing E2 (n = 6) or sham implant (n = 1); then every 6 h up to 54 h post-treatment. For the first 12 h PR depression in the control was identical to controls in the acute experiment; after 36 h PR was similar to pretreatment levels. In E2 implanted animals PR fell to a mean of 1.8 plus or minus 0.1 ng/ml, 4-12 h after implantation, then recovered, stabilizing at 2.3 plus or minus 0.1 ng/ml after 18 h. It is concluded that estrogen treatment rapidly causes a depression of pituitary response to exogenous LH-RH. This rapid effect may not be dependent on E2 dosage. The extent of recovery of pituitary responsiveness probably depends upon the level and persistence of the E2 treatment.
D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D011863:Radioimmunoassay; D013552:Swine; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone