Progesterone and regulation of the follicle-stimulating hormone (FSH-beta)gene

Progesterone (P) biphasically modulates follicle-stimulating hormone (FSH) secretion in the mt both in vivo and in vitro with the duration of estrogen priming determining the biphasic nature of the P action, probably through estrogen up-regulation of the anterior pituitary progesterone receptor (PR) levels. P has been also shown to regulate anterior pituitary levels of FSH -beta mRNA in the rat. Although the mechanism of this action has not been d etermined, steroids may regulate gene expression through the binding of lig anded receptors to gene sequences known as hormone response elements (HRE); however, it is not known whether HRE's exist on the rat FSH-beta gene. We have localized a series of progesterone response elements (PRE) sequences o n the rat FSH-beta gene and have begun testing the hypothesis that P modula tes the expression of the rat FSH-beta gene through the direct binding of t he P/PR complex to these PRE-like sequences. Electromobility shift assays i ndicate that these PRE-like sequences bind PR with high affinity and specif icity. Tn addition, when a 361-base pair sequence, which contains the three PRE-like sequences localized in the upstream region of the gene, was clone d into a luciferase expression vector driven by a heterologous promoter and transiently transfected into anterior pituitary cell cultures, progestin s timulation elicited increased luciferase expression. These results indicate d that the 361-base pair sequence conferred P-responsiveness to a heterolog ous promoter. The data further suggest that FSH synthesis in the rat is mod ulated by direct binding of PR to PRE-like sequences. (C) 1999 Elsevier Sci ence inc. All rights reserved.