The glycoprotein alpha-subunit is critical for secretion and stability of the human thyrotropin beta-subunit.
TSH is a member of a family of heterodimeric glycoprotein hormones which have a common alpha-subunit but differ in their hormone-specific beta-subunit. To study the posttranslational processing and assembly of human TSH, eukaryotic expression vectors were constructed that contained either the human TSH beta gene only or both the TSH beta and alpha-genes. These vectors were transfected into Chinese hamster ovary cells and stable cell lines synthesizing TSH beta or TSH dimer were isolated. The kinetics of secretion of TSH beta and the rate of assembly of TSH dimer were compared to the known secretion and assembly of human LH and human CG. In the absence of the alpha-subunit, CG beta is secreted efficiently, but TSH and LH beta-subunits are slowly degraded intracellularly (t1/2 approximately equal to 6 h) and less than 10% is secreted into the medium. In the presence of the alpha-subunit CG beta was also secreted efficiently as dimer but only 50% of the LH beta appeared in the medium as LH dimer. However, unlike LH beta, the alpha-subunit efficiently combines with TSH beta since greater than 95% was secreted as TSH dimer. Thus, the determinants for human TSH beta secretion and assembly are unique from the other human glycoprotein hormone beta-subunits.
Matzuk
M M
MM
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Kornmeier
C M
CM
Whitfield
G K
GK
Kourides
I A
IA
Boime
I
I
D000818:Animals; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D005260:Female; D005822:Genetic Vectors; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism; D013972:Thyrotropin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D006063:Chorionic Gonadotropin; D006023:Glycoproteins; D007986:Luteinizing Hormone; D013972:Thyrotropin