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Acute and Chronic Estradiol-17β Inhibition of LH Release in Prepubertal Female Pigs: Time Course and Site of Action¹

Animal Genetics Laboratory, University of Illinois Urbana IL 61801

Abstract

It has been demonstrated that 5.0 µg estradiol-17β (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 (LH) by RIA after iv injection of 2.0 µg 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 ± 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 < 0.005) 1 h following E₂ (LH = 1.0 ± 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 ± 0.1 ng/ml, 4–12 h after implantation, then recovered, stabilizing at 2.3 ± 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. (Endocrinology 96: 558, 1975)

Footnotes

¹ This study was supported by Grants NIH HD 3043 and the Ford Foundation.

² Department of Physiology, University of Western Ontario, London, Ontario, Canada.

³ Department of Physiology and Environmental Studies, Nottingham University School of Agricultural Sciences, Sutton Bonington, Loughborough, Leicestershire, England.

⁴ To whom reprint requests should be addressed.

Received May 29, 1974.