Opposite Effects of Prolactin (Prl) on the Expression of Aromatase and Liver Receptor Homolog 1 (LRH-1) in Luteal Cells.

Abstract

. effects are mediated in part by an increase in the expression of the estrogen receptors (2), which, in turn, are needed for estradiol action. Paradoxically, it has been shown that prolactin blocks the stimulation of estradiol production by FSH in granulosa cells (3, 4) and inhibits aromatase expression in the corpus luteum (5, 6). This inhibitory effect of Prl on estradiol production explains why low levels of aromatase expression are found in corpora lutea during early gestation when surges of prolactin are being released twice daily from the pituitary. However, there is no direct evidence indicating that pituitary prolactin in fact inhibits luteal aromatase at the beginning of pregnancy in the rat. In addition, the mechanism involved in the inhibition of aromatase expression by Prl is not known. In all species studied thus far the aromatase gene is controlled by at least two Figure 1Effect of the Inhibition of Prl Secretion on the Expression of Figure 4: Reversibility of the Inhibitory Effect of Prl. Luteal cells were cultured in the , promoters. We have demonstrated that the promoter located immediately upstream of the coding region, also known as the proximal promoter, controls the expression of aromatase in luteal cells (7, 8). The proximal promoter contains a cAMPresponsive element-like sequence (CLS) and two binding sites for members of the nuclear receptors 5A family of transcription factors (NR5a/SF-1 and NR5b/LRH-1) (9). This promoter also contains a response element for members of the GATA family of transcription factors and one AP-3 binding site. These binding sites are highly conserved between species. Of the factors that bind to these sites, LRH-1, SF-1, and GATA4 seem to play an important role in the regulation of aromatase in granulosa and luteal cells (Reviewed in 9). In this report we examined the regulation of aromatase by Prl in the corpus luteum Aromatase in the Corpus Luteum of Rats on Day 5 of Pregnancy. On day 4 of pregnancy, rats were treated with Prl or Vehicle 30 minutes before the administration of Ergocriptine (ERGO), an inhibitor of Prl secretion. Luteal aromatase expression was determined 24 hours after the administration of ERGO. Columns with different letter differ significantly. Figure 6: Expression of Aromatase, LRH-1, and SF-1 in the Rat Corpus Luteum during Pregnancy. absence (Control) or presence of Prl (1 ug/ml) for 10 days. On the 10th day, Prl was removed from the medium and the cells incubated for 12, 24, or 48 hours more. Aromatase expression was determined by RT-PCR. Columns with different letters differ significantly.