Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms

Abstract

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG.

PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus

“…The IGFs are crucial to the uterine restoration processes. It is demonstrated that IGFs promote proliferation of uterine cells through activation of the mitogen‐activated protein kinases (MAPK) pathway which can be reversed by the neutralizing antibody that is against the IGF receptor (IGF‐IRβ) in vitro . VEGF is a key regulator of angiogenesis and vascular function.…”

Splenic Leiomyoma in Dog

“…Rarely this types of tumors can be localized in the kidney [5], the third eyelid [6] or the heart [7]. In women of reproductive age, leiomyoma is one of the most common tumors of the myometrium, but the etiology of these tumors is not understood [8], [9].…”

“…It often appears as a fibroleiomyoma [8]. Usually, it exhibits small amounts of stromal connective tissue (leiomyoma molle), occasionally in firm formations (leiomyoma durum).…”

“…Additionally, human chorionic gonadotropin may participate in leiomyoma development in pregnant women. Some leiomyomas have a genetic etiology [8]. Clinical signs of leiomyoma are not specific and may be poorly expressed.…”

“…While analyzing histological samples, one can observe multidirectional arrangement of muscle fibers, that are characteristic for leiomyomas which contrast with normal, healthy smooth muscle tissue that has regular structure [2]. Proliferating smooth muscle cells are surrounded by pseudo-capsule and the leiomyoma mass demonstrates much more deposition into the extracellular matrix (more collagen than normal smooth muscle tissue) [8]. The origins of leiomyoma are most probably the undifferentiated perivascular cells, or the muscular layer of organ in which it occurs.…”