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Estrogen-Stimulated Deoxyribonucleic Acid Synthesis: A Ratchet Model for the Prereplicative Period^*

GARY STACK and JACK GORSKI

Department of Biochemistry, College of Agricultural and Life Sciences, Univerity of Wisconsin-Madison Madison, Wisconsin 53706

Address requests for reprints to: Dr. Jack Gorski, Department of Biochemistry, 420 Henry Mall, University of Wisconsin, Madison, Wisconsin 53706.

Abstract

Multiple injections of a short acting estrogen, l,3,5(10)-estratriene-3,16-diol (16-E₂), have been used to analyze the lag or prereplicative period of approximately 12 h, which precedes the onset of estrogen-stimulated DNA synthesis. A single injection of 1.0 µg 16-E₂, which itself does not stimulate DNA synthesis, shortened by 3–4 h the lag period between subsequently administered estrogen and the initiation of DNA synthesis. This lag-shortening effect of 16-E₂ was stable for 24 h, but had decayed by 36 h. One or two additional injections of 16-E₂ given sequentially at 3-h intervals each further shortened the lag period but to a lesser extent than the first injection. The results indicate that estrogen induces the accumulation of relatively stable cell changes which are required for the onset of DNA synthesis. The prolonged estrogen requirement during the lag period is not truly discontinuous as previously suggested but rather can be satisfied by discontinuous pulses of estrogen in a ratchet-like fashion because of the stability of their effects. (Endocrinology 117: 2017–2023, 1985)

Footnotes

^* This work was supported in part by the College of Agricultural and Life Sciences, The University of Wisconsin, Madison; NIH Grant HD-08192, Ford Foundation Fund, 1 T32 07007, and a predoctoral fellowship under PHS Award 07215.

Present address: Laboratoire de Génétique Moléculaire des Eukaryotes du CNRS, Unité 184 de l’INSERM et Institut de Chimie Biologique, Faculté de Médecine, 67085 Strasbourg, France.

Received April 17, 1984.

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