Progesterone and the control of uterine cell proliferation and differentiation

Abstract

Progesterone is the only steroid hormone that is essential for the establishment and maintenance of pregnancy in all mammalian species that have been studied. Mice lacking the progesterone receptor (PR) by targeted mutagenesis exhibit abnormalities in all aspects of reproduction including sexual behavior, mammary gland development, ovulation, and implantation. Implantation in PR null mice fails, in part, because the uterine stromal cells cannot undergo differentiation (the decidual cell reaction). Uterine stromal cells do not divide without progesterone and proliferation is blocked by progesterone antibodies and PR antagonism. In spite of the preeminence of progesterone in female reproduction, its molecular mechanisms of action on target cell proliferation and differentiation are not well understood. Recent studies suggest that progesterone plays a direct role in regulating cell cycle transit by increasing the expression and activation of cell cycle regulatory complexes. Furthermore, this progesterone-dependent regulation of cell cycle transit may provide a unique window of opportunity for uterine stromal cells to exit the proliferative cycle, and if exposed to appropriate agents, enter into the differentiation pathway.

Alternative farnesoid structures induce different conformational outcomes upon the Drosophila ortholog of the retinoid X receptor, ultraspiracle

“…Among the many hormone-regulated processes are those developmental decisions in tissue commitment and differentiation that are controlled in vertebrates by steroids (Rider 2002;Manolagas et al, 2002) and the terpenoid-derived retinoids (Maden, 2001;Underhill et al, 2001;Smith et al, 1998;Villarroya et al, 1999). Developmental decisions in the invertebrates also appear to be regulated by steroids (Buszczak and Segraves, 2000;Thummel, 2000) and terpenoid-derived farnesoids (Truman and Riddiford, 2002;Jones, 1995).…”

Progesterone Receptor Transactivation of the Secretory Leukocyte Protease Inhibitor Gene in Ishikawa Endometrial Epithelial Cells Involves Recruitment of Krüppel-Like Factor 9/Basic Transcription Element Binding Protein-1

“…Our findings define a novel pathway for BTEB1/PR cross-talk to facilitate P-dependent gene transcription in endometrial epithelial cells. (Endocrinology 147: 1969(Endocrinology 147: -1978(Endocrinology 147: , 2006 T HE STEROID HORMONE progesterone (P) plays essential roles in uterine endometrial growth and differentiation (1)(2). It classically acts through two progesterone receptor (PR) isoforms, PR-A and PR-B, which in the human and mouse are encoded by a single gene (3,4).…”

Proteomic analysis of the sheep caruncular and intercaruncular endometrium reveals changes in functional proteins crucial for the establishment of pregnancy

“…Prior to the initial development of the fertilised ovum to the blastocyst stage, the preparation of a receptive endometrium through the actions of progesterone (Rider 2002) and oestradiol ) is a prerequisite for the extraembryonic membranes-endometrial dialogue that supports conceptus attachment, implantation, development and survival (Imakawa et al 2004, Spencer et al 2004. In addition to the endometrial changes before implantation, other implantation and post-implantation changes in the endometrium may result from in utero presence of a conceptus.…”