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Effects of 2-Hydroxyestradiol-17β, 2-Hydroxyestradiol-17, and 4-Hydroxyestrone on the Preovulatory Luteinizing Hormone Surge in the Rat: Agonist and Antagonist Actions^*

YUJI OKATANI and JACK FISHMAN

The Rockefeller University, New York New York 10021

Address requests for reprints to: Dr. Jack Fishman, The Rockefeller University, 1230 York Avenue, New York, New York 10021.

Abstract

Four-day cycling rats equipped with intracardiac catheters were injected with 2-hydroxyestradiol-17β (2OHE₂-17β) at 0800, 0900, 1000, and 1200 h on the morning of proestrus. The administration at 0800 and 0900 h resulted in abolition of the afternoon preovulatory LH surge in virtually all animals. Injections given at 1000 and 1200 h were ineffective in this respect. The isomeric catechol estrogen 4-hydroxyestrone effectively inhibited the LH surge when given at 0900 h, but not if injected at 1000 or 1200 h. In contrast, the nonestrogenic 2-hydroxyestradiol-17 was effective in blocking the LH surge when given at 0900 or 1000 h. Rats treated with 2OHE₂-17β at 1000 h responded normally to exogenous LHRH adminstration in the afternoon, indicating that the action of 2OHE₂-17β is at the hypothalamic level. 2OHE₂-17β and 4-hydroxyestrone, which are potent estrogens, may act in this instance first as estrogen agonists, advancing the "time window" when their catechol antagonist properties in blocking the LH surge can be functional. The nonuterotropic 2-hydroxyestradiol-17 and 2-hydroxyestrone act solely as catechol estrogens and inhibit the preovulatory LH surge if administered at a time when they be present during this physiological window, which is thought to involve events at the estrogen-catecholaminergic interphase. (Endocrinology 115: 1090–1094, 1984)

Footnotes

^* This work was supported by Grant HD-16422 from the NICHHD, Grant CA-22795 from the NCI, and funds from The Rockefeller Foundation.

Present address: Department of Obstetrics and Gynecology, Kochi Medical School, Oko, Nankoku, Kochi, 781-51 Japan.

Received October 5, 1983.