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The Glycoprotein -Subunit is Critical for Secretion and Stability of the Human Thyrotropin β-Subunit

M. M. Matzuk^*, C. M. Kornmeier, G. K. Whitfield, I. A. Kourides and I. Boime

Departments of Pharmacology and Obstetrics and Gynecology, Washington University School of Medicine St. Louis, Missouri 63110
Laboratory of Molecular Endocrinology, Memorial Sloan-Kettering Cancer Center and Cornell University Medical College New York, New York 10021

Address requests for reprints to: Dr. Irving Boime, Department of Pharmacology, University of Washington School of Medicine, Box 8103, 660 South Euclid Avenue, St. Louis, Missouri 63110.

Abstract

TSH is a member of a family of heterodimeric glycoprotein hormones which have a common -subunit but differ in their hormone-specific β-subunit. To study the posttranslational processing and assembly of human TSH, eukaryotic expression vectors were constructed that contained either the human TSHβ gene only or both the TSHβ and -genes. These vectors were transfected into Chinese hamster ovary cells and stable cell lines synthesizing TSHβ or TSH dimer were isolated. The kinetics of secretion of TSHβ 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 -subunit, CGβ is secreted efficiently, but TSH and LHβ-subunits are slowly degraded intracellularly (t, 6 h) and less than 10% is secreted into the medium. In the presence of the -subunit CGβ was also secreted efficiently as dimer but only 50% of the LHβ appeared in the medium as LH dimer. However, unlike LHβ, the -subunit efficiently combines with TSHβ since greater than 95% was secreted as TSH dimer. Thus, the determinants for human TSHβ secretion and assembly are unique from the other human glycoprotein hormone β-subunits.

FOOTNOTES

This research was supported in part by the Monsanto Company and NIH Grants HD-20197 (to I.B.) and CA-23185 (to I.A.K.).

^* Participant in the Medical Scientist Training Program supported in part by Grant HL-07275 from the National Heart, Lung, and Blood Institute and National Institute of General Medical Sciences Grant GM-08200.

Present address: Department of Biochemistry, University of Arizona, Tuscon, AZ 85724.

Received for publication October 15, 1987. Accepted for publication November 24, 1987.

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