Progesterone inhibitory role on gastrointestinal motility

Abstract

Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders.

Fig. 1

Progesterone mechanism of action. The classical pathway involves the nuclear progesterone receptor (nPR) dimerization and translocation to the nucleus to induce genomic effects via activating or inhibiting gene transcription. The non-classical pathway is rapid action that involves membrane progesterone receptor (mPR) and the subsequent activation of several second messengers such as elevation of intracellular calcium (Ca²⁺), extra-cellular signal-regulated kinases (ERK) and Protein kinase B (AKT)

Fig. 2

Effect of progesterone on gut smooth muscle contraction: Progesterone activates its cell surface receptors (mPR), PR that leads to NO production. NO production leads to the generation of cGMP from GTP and in turn activation of PKG. PKG acts to inhibit signaling pathways that provoke contraction such as RhoK and activates the signaling that leads to muscle relaxation such as MLCP. mPR: progesterone receptor, NO: Nitric oxide, cGMP: cyclic guánosine monophosphate, GTP: guanosine triphosphate, PKG: protein kinase G, RhoK: Rho kinase, MLCP: myosin light chain phosphatase