Dr. Ron’s Research Review – August 17, 2016

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This week’s research review focuses on hCG and cancer.

hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. (Cole, 2012b)

The term human chorionic gonadotropin (hCG) refers to a group of 5 molecules (hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta), each sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure. (Cole, 2012a)
hCG and sulfated hCG are hormones produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells. These molecules simulate hCG/LH receptor (to produce progesterone) and are central to human menstrual cycle and human pregnancy.
Hyperglycosylated hCG is an autocrine produced by placental cytotrophoblast cells. Hyperglycosylated hCG antagonizes TGF-beta receptor, which drives malignancy in placental cancers, and in testicular and ovarian germ cell malignancies.
While hCG may appear like only a hormone associated with pregnancy, it is not, and may be at the center of cancer research.

 

Dr. Ron


 

Articles

Biological functions of hCG and hCG-related molecules.
            (Cole, 2010) Download
BACKGROUND:  hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. RESULTS AND DISCUSSION:  hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

HCG variants, the growth factors which drive human malignancies.
            (Cole, 2012a) Download
The term human chorionic gonadotropin (hCG) refers to a group of 5 molecules, each sharing the common amino acid sequence but each differing in meric structure and carbohydrate side chain structure. The 5 molecules are each produced by separate cells and each having separate biological functions. hCG and sulfated hCG are hormones produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells. Hyperglycosylated hCG is an autocrine produced by placental cytotrophoblast cells. Hyperglycosylated hCG drives malignancy in placental cancers, and in testicular and ovarian germ cell malignancies. hCGβ and hyperglycosylated hCGβ are autocrines produce by most advanced malignancies. These molecules, particularly the malignancy promoters are presented in this review on hCG and cancer. hCGβ and hyperglycosylated hCGβ are critical to the growth and invasion, or malignancy of most advanced cancers. In many ways, while hCG may appear like a nothing, a hormone associated with pregnancy, it is not, and may be at the center of cancer research.

hCG, the wonder of today's science.
            (Cole, 2012b) Download
BACKGROUND:  hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. CONTENT:  These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. CONCLUSIONS:  The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death.

 

 

References

Cole, LA (2010), ‘Biological functions of hCG and hCG-related molecules.’, Reprod Biol Endocrinol, 8 102. PubMed: 20735820
——— (2012a), ‘HCG variants, the growth factors which drive human malignancies.’, Am J Cancer Res, 2 (1), 22-35. PubMed: 22206043
——— (2012b), ‘hCG, the wonder of today’s science.’, Reprod Biol Endocrinol, 10 24. PubMed: 22455390