HCG(Human chorionic gonadotrophin)

 

HCG, or human chorionic gonadotropin, is a glycoprotein hormone produced by

 

During pregnancy HCG is secreted by the syncytial  trophbast cells into the fluids of the mother  and can be detected in the mother's blood or urine . This hormone is what we look for with a "pregnancy test".

HCG is first detectable in the blood as early as 7-8 days after ovulation,shortly after the blastocyst implants in the endometrium by  sensitive HCG assays. 85% of normal pregnancies will have the HCG level double every 72 hours and reach a maximum level in about 10 to 12 weeks. It decreases to a much lower value by 16 to 20 weeks after ovulation and continues at this level for the remainder pregnancy.


 

HCG is a glycoprotein having a molecular weight of about 39,000 and has pretty similar molecular structure and function as LH secrted by the pituitary. During pregnancy the most important  function is to prevent the normal involution of the corpus luteum at the end of cycle. Insead it causes the corpus luteum to secrete larger quantities of its usual sex hormones , estrogen and progesterone. These sex hormone prevent menstruation and cause the endometrium to continue growing  and store large amount of nutrients. Under the influemnce of HCG the corpus luteum grows to about twice the size of its intial size by four weeks after the pregnanacy begins and its continued secretion of estrogen and and progesterone maintains the decidual nature of the endometrium which is necessary for the early development of fetus. If the corpus luteum is removed before 7th  week of pregnancy, spontaneous abortion almost always occur. After 12 weeks placenta itself secretes sufficient quantities of progeserone and estrogen to maintain pregnancy for remainder of he gestation period, the corpus luteum slowly involutes after the 13th 17th week of gestation.

 

PREGNANCY STATUS SERUM hCG LEVELS

An hCG level of less than 5 mIU/ml generally indicates you are not pregnant.

from conception

from LMP

(mIU/ML or IU/L)

7 days

3 weeks

0 to 5

14 days

28 days

3 to 426

21 days

35 days

18 to 7,340

28 days

42 days

1080 to 56,500

35 - 42 days

49 - 56 days

7,650 to 229,000

43 - 64 days

57 - 78 days

25,700 to 288,000

57 - 78 days

79 - 100 days

13,300 to 253,000

17 - 24 weeks

2nd trimester

4060 to 65,400

25 wks to term

3rd trimester

3640 to 117,000

After several days postpartum

 

nonpregnant levels (<5)"

  

"Results in Twin Gestation"

"Quanitative serum hCG tests detect multiple pregnancy approximately 9 weeks earlier than ultrasound. One small study (Jovanovic, 1977) found hCG levels in 15 singleton and 9 twin pregnancies were as follows:

DAYS FROM LMP

hCG in SINGLTON AVERAGE

GESTATION RANGE

hCG in AVERAGE

TWIN GESTATION RANGE

28

64.7

9.4 to 120

64.7

9.5 to 120

33

450

300 - 600

1,500

200 to 1,800

36

1,500

1,200 - 1,800

19,200

2,400 to 36,000

40

3,600

2,400 - 4,800

58,344

8,700 to 108,000

45

36,000

12,000 - 60,000

126,000

72,000 to 180,000

70

120,000

96,000 - 144,000

414,000

348,000 to 480,000"

 There is a large variation in a "normal" HCG level for any given time in pregnancy but commonly

 Greater-than-normal levels may indicate:

        choriocarcinoma of the uterus

        ectopic pregnancy

        hydatidiform mole of the uterus

        normal pregnancy

        ovarian cancer

        testicular cancer

 

Lower-than-normal levels may indicate:

        dead fetus

        incomplete miscarriage

        threatened spontaneous abortion

 
    hCG is a heterodimeric glycoprotein with a total molecular  weight of 39,000 consist  of two subunits, alpha and beta, held together by ionic and hydrophobic forces. The alpha-subunit is a glycopeptide of 92 amino acids, with asparagine-linked (N-linked) sugar moieties attached at residues 52 and 78. It is stabilized by 5 disulfide linkages.

The -subunit of hCG is a glycopeptide of 145 amino acids, stabilized by 6 disulfide linkages. It has N-linked sugar moieties attached at residues 13 and 30, and 4 serine-linked (O-linked) sugar moieties attached to the C-terminal peptide (-subunit residues 121-145). The -subunits of the glycoprotein hormones are unique, giving them their different biological characteristics.

  



 

Normal trophoblast hCG molecules (normal pregnancy) have mono and biantennary type N-linked sugar moieties and simple disaccharide-core O-linked sugar units. Trophoblast disease hCG molecules (persistent mole and choriocarcinoma) and germ cell and other cancer hCG molecules can be made with more-complex sugar side chains, triantennary N-linked sugar moieties and tetrasaccharide core O-linked sugar moieties . This type of hCG we call hyperglycosylated hCG or ITA (Invasive Trophoblast Antigen). The N-linked sugar side chains on pituitary hCG have unusual sulfated sugar moieties.

In addition to intact  alpha-beta dimmer hCG, free hCG subunits (free alpha-subunit and free Beta-subunit) are produced in pregnancy, trophoblast disease and cancer. These can be detected in serum, plasma and urine samples.

Free subunits can derive from the excess synthesis of alpha or beta subunit or incomplete combination of subunits in cells. Excess alpha subunit which fails to get incorporated in hCG may become hyperglycosylated (like trophoblast disease and cancer hCG) with extra sugar residues on the N-linked sugar moieties . This is called large free alpha-subunit. This can also be detected in plasma, serum and urine samples.

Free subunits also derive from the slow dissociation of hCG, dissociation half-time >40 days at 37 deg, and from the more rapid dissociation of nicked, damaged or hyperglycosylated hCG, dissociation half-time 10-16 days .  A nicked or cleaved hCG is produced. Nicked hCG is most evident in serum and urine samples in the later trimesters of pregnancy. It may be the principal form of hCG detected in choriocarcinoma patients, and in germ cell and other cancer cases. nicked hCG is cleaved or cut in the -subunit peptide between residues 47 and 48. It can be cleaved between residues 43 and 44 or 44 and 45 in some choriocarcinoma cases  Although cleaved, the molecules are held together by the intra-peptide disulfide linkages; no amino acids or sugar residues are missing . Nicking occurs by the action of proteolytic enzymes in the placental, mole or cancer tissue, or in the circulation.