Estrogen Regulation of Prolactin Gene Transcription in Vivo: Paradoxical Effects of 17β-Estradiol Dose*

Abstract

We investigated in male rats the effects of a range of doses of 17 beta-estradiol on PRL gene transcription, the level of circulating estradiol, and the levels of nuclear and cytosolic forms of the anterior pituitary estrogen receptor. One hour after 17 beta-estradiol injection, transcription of the PRL gene was significantly stimulated by 0.1 micrograms and maximally stimulated by 1.0 microgram/animal. Lesser stimulatory effects were observed 1 h after injection of 10 or 100 micrograms. At this 1 h point, the level of circulating estradiol was linearly increased relative to the 17 beta-estradiol dose. The level of nuclear form estrogen receptor was increased from 8% of the total receptor content in control rats to 12%, 28%, 50%, and 64% of the total receptor content in rats that received 0.1, 1.0, 10.0, and 100 micrograms, respectively. The anterior pituitaries of rats injected with 100 micrograms 17 beta-estradiol contained 30% fewer measurable estrogen receptors than control rats. Thus, dose-dependent losses of transcriptional responsiveness and measurable estrogen receptor were observed 1 h after injection of the larger doses of 17 beta-estradiol. Twenty-four hours after injection of the various doses of 17 beta-estradiol, PRL gene transcription was stimulated 1.3-fold in response to 0.1 microgram and approximately 2-fold in response to 1.0, 10, and 100 micrograms. At the 24 h point the circulating level of this hormone and the levels of nuclear and cytosolic forms of the estrogen receptor had returned to near their control values. This differing dose responsiveness at 1 and 24 h supports our previously reported observation that estrogen regulates PRL gene transcription in vivo through at least two independent mechanisms.