Sulfated Pituitary hCG

The pituitary gland in men and woman produces a small concentration of sulfated hCG. Sulfated means that some oligosaccharide sugar sugar side chains terminate with a sulfate residues instead of the acidic sugar residue sialic acid. Sulfated hCG is made by pituitary gonadotrope cells, the cells that make luteinizing hormone (LH) and follicle stimulating hormone (FSH). Examining the gene on chromosome 19, 8 back to back genes all code for hCG ß-subunit, and one on the end codes for LH ß-subunit. To make pituitary LH, the hypothalamic hormone gonadotropin releasing hormone (GnRH) acts on this solitary end LH ß-subunit gene to promote LH production. It appears that it incidentally also promotes the neighboring hCG ß-subunit genes and sulfated hCG is made. Both hCG ß-subunit and LH ß-subunit rapidly associate with the excess of common alpha subunit to form hCG and LH dimeric hormone.

Science papers shows that sulfate hCG accounts for approximately 1/50th of the LH concentration made by the pituitary gland in males and females. The problem is that Birken et al. showed that sulfated hCG is approximately 50-fold more potent that pituitary LH. As such, the two hormones produced by pituitary gonadotrope cells both have equal activities at the joint LH/hCG receptors in promoting steroidogenesis in men and women, promoting progesterone (luteal phase of menstrual cycle) and androstenedione (follicular phase) in women and testosterone in men. In women, it is fair to say that both sulfated hCG and LH promote ovulation.

When a woman reaches peri-menop and menopause her ovaries produce reduced amounts of estrogens or stops producing estrogen. With the limited estrogen feedback to the hypothalamus, stronger and stronger pulses of GnRH are made by the hypothalamus and act on the pituitary gonadotrope cells. As a result, sky high levels of FSH and LH are made by the pituitary gonadotrope cells at this time. While the low levels of sulfated hCG are hardly detectable during the menstrual cycle, the higher levels produced in menopause are very detectable (up to serum concentration of 39 mIU/ml). This is a cause of hCG production outside of pregnancy. Pituitary production of sulfated hCG is completely harmless and completely natural and needs no therapy of any kind.

The best proof that the hCG detected is coming from the pituitary is showing that the FSH concentration is unusually high (>30 mIU/ml). Otherwise a physician can prove that the hCG is coming from the pituitary by placing a patient on a high estrogen oral contraceptive pill for 3 weeks. If the hCG is coming from the pituitary, this will suppress pituitary hCG production.

Cole LA. Sasaki Y, Muller CY. Normal production of human chorionic gonadotropin in
menopause. New Engl J Med 2007;356:1184-1186.

Cole LA, Laidler LL, Muller CY. USA hCG Reference Service 10-year report. Clin Biochem 2010;43:1013-1022.