Glycoprotein hormones

 

Glycoprotein Hormones:-

The glycoprotein hormone family includes TSH, and the two gonadotropins. The three glycoprotein hormones are synthesized and stored in pituitary basophils and, as their name implies, each contains sugar moieties covalently linked to asparagine residues in the polypeptide chains. All three are comprised of two peptide subunits, designated alpha and beta, which, though tightly coupled, are not covalently linked. The alpha subunit of all three hormones is identical in its amino acid sequence, and is the product of a single gene located on chromosome 6.But the  beta subunits of each are somewhat larger than the alpha subunit and confer physiological specificity. Both alpha and beta subunits contribute to receptor binding and both must be present in the receptor binding pocket to produce a biological response. Beta sub­units are encoded in separate genes located on different chromosomes:for example :- TSH β on chromosome 1, FSH β on chromosome 11, and LH β on chromosome 19, but there is a great deal of homology in their amino acid sequences. Both subunits contain carbohydrate moieties that are considerably less constant in their composition than are their peptide chains. Alpha subunits are synthesized in excess over beta subunits, and hence it is synthesis of beta subunits that appears to be rate-limiting for production of glycoprotein hormones. Pairing of the two subunits begins in the rough endoplasmic reticulum and continues in the Golgi apparatus, where processing of carbohydrate components of the subunits is completed. The loosely paired complex then undergoes spontaneous refolding in secretory granules into a stable, active hormone. Control of expression of the alpha and beta subunit genes is not perfectly coordinated, and free alpha and the beta subunits of all three hormones may be found in blood plasma.

 The glycoproteins. The placental hormone, human chorionic gonadotropin (hCG), is closely related chemically and functionally to the pituitary gonadotropic hormones. It, too, is a glycoprotein and consists of an alpha and a beta chain. The alpha chain is a product of the same gene as the alpha chain of pituitary glyco-protein hormones. The peptide sequence of the beta chain is identical to that of LH except that it is longer by 32 amino acids at its carboxyl terminus.

 

Curiously, although there is only a single gene for each beta subunit of the pituitary glyco-protein hormones, the human genome contains 7 copies of the hCG beta gene, all located on chromosome 19 in close proximity to the LH beta gene. Not surprisingly, hCG has biological actions that are similar to those of LH, as well as a unique action on the corpus luteum