This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frick, G. P. Articles by Goodman, H. M. Search for Related Content PubMed PubMed Citation Articles by Frick, G. P. Articles by Goodman, H. M.

Tissue Distribution, Turnover, and Glycosylation of the Long and Short Growth Hormone Receptor Isoforms in Rat Tissues¹

Department of Physiology (G.P.F., L.-R.T., H.M.G.), University of Massachusetts Medical School, Worcester, Massachusetts 01655; and Molecular and Cellular Biology Group (W.R.B.), American Cyanamid, Princeton, New Jersey 08540

Address all correspondence and requests for reprints to: H. Maurice Goodman, Ph.D., Department of Physiology, University of Massachusetts Medical School, 55 Lake Avenue, North, Worcester, Massachusetts 01655-0127.

Two isoforms of the GH receptor, the full-length receptor (GHR_L) and a short isoform (GHR_S) that lacks the transmembrane and intracellular domains of GHR_L, have been analyzed in rat tissue extracts by Western blotting and immunoprecipitation. Although quantitative estimates of GHR_S and GHR_L based on coprecipitation of [¹²⁵I]GH indicated similar amounts of both isoforms in tissue extracts, the 110 kDa band corresponding to GHR_L was generally not detected on Western blots without enrichment by immunoprecipitation. Two bands with electrophoretic mobilities corresponding to 38 and 42 kDa were present in extracts prepared from liver, muscle, and adipocytes. Western blots of the GH binding protein in rat serum also revealed two bands, but these had electrophoretic mobilities corresponding to 44 and 52 kDa. After digestion by endoglycosidase F, a single band with an electrophoretic mobility corresponding to 31 kDa was detected in samples from adipocytes, liver or serum, indicating that GHR_S retained in tissues is glycosylated less extensively than that in rat serum. Digestion with neuraminidase indicated that the smaller glycoproteins in tissue extracts lack sialic acid residues that are present in serum samples. Furthermore, endoglycosidase H degraded GHR_S in liver extracts to a 31 kDa band but did not degrade serum samples, suggesting that tissues retain a high mannose form of GHR_S. The abundance of GHR_S or GHR_L in tissues from male, virgin female, and pregnant rats was estimated from the amount of ¹²⁵I-GH that was bound to each isoform after immunoprecipitation. Liver contained more than 10 times as much GHR_S per gram of tissue as fat or muscle. In liver, muscle, and fat, the amount of GHR_S exceeded that of GHR_L, sometimes by as much as 6-fold. GHBP levels in serum of females exceeded those in males, and rose even higher in pregnant females. The abundance of GHR_S in all tissue extracts paralleled serum levels. In muscle and fat, the levels of GHR_L did not differ in male, female and pregnant rats, whereas in liver, the pattern was similar to the GHR_S pattern. In all tissues, pools of GHR_S exceeded those of GHR_L by a factor that grew larger as tissue and serum levels increased.

The half life of GHBP in serum was estimated to be 2.4 h in rats treated with cycloheximide, whereas that of GHR_S was 20 min in liver and 8.5 h in fat. These results suggest that GHR_S is synthesized in liver 8 times faster than it is released into serum, whereas synthesis in fat is less than 30% of the rate at which it is released into serum by all tissues. Therefore, liver appears to be the major source of GHBP in serum. Although secretion into the circulatory system accounts for little or perhaps none of its turnover in some tissues, GHR_S pools in tissues do appear to be regulated, suggesting that GHR_S may function primarily in the cells in which it is synthesized.

This article has been cited by other articles:

				H. Jiang, Y. Wang, M. Wu, Z. Gu, S. J. Frank, and R. Torres-Diaz Growth Hormone Stimulates Hepatic Expression of Bovine Growth Hormone Receptor Messenger Ribonucleic Acid through Signal Transducer and Activator of Transcription 5 Activation of a Major Growth Hormone Receptor Gene Promoter Endocrinology, July 1, 2007; 148(7): 3307 - 3315. [Abstract] [Full Text] [PDF]

				J G Miquet, A I Sotelo, F P Dominici, M S Bonkowski, A Bartke, and D Turyn Increased sensitivity to GH in liver of Ames dwarf (Prop1df/Prop1df) mice related to diminished CIS abundance J. Endocrinol., December 1, 2005; 187(3): 387 - 397. [Abstract] [Full Text] [PDF]

				H. K. Gleeson, C. A. Lissett, and S. M. Shalet Insulin-Like Growth Factor-I Response to a Single Bolus of Growth Hormone Is Increased in Obesity J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1061 - 1067. [Abstract] [Full Text] [PDF]

				D. Cifone, F. P. Dominici, V. G. Pursel, and D. Turyn Inability of heterologous growth hormone (GH) to regulate GH binding protein in GH-transgenic swine J Anim Sci, July 1, 2002; 80(7): 1962 - 1969. [Abstract] [Full Text] [PDF]

				M. Bondanelli, A. Margutti, M. R. Ambrosio, L. Plaino, L. Cobellis, F. Petraglia, and E. C. degli Uberti Blood Growth Hormone-Binding Protein Levels in Premenopausal and Postmenopausal Women: Roles of Body Weight and Estrogen Levels J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1973 - 1980. [Abstract] [Full Text]

				C. Phornphutkul, G. P. Frick, H. M. Goodman, S. A. Berry, and P. A. Gruppuso Hepatic Growth Hormone Signaling in the Late Gestation Fetal Rat Endocrinology, October 1, 2000; 141(10): 3527 - 3533. [Abstract] [Full Text] [PDF]

				Y. Mao, P.-R. Ling, T. P. Fitzgibbons, K. C. McCowen, G. P. Frick, B. R. Bistrian, and R. J. Smith Endotoxin-Induced Inhibition of Growth Hormone Receptor Signaling in Rat Liver in Vivo Endocrinology, December 1, 1999; 140(12): 5505 - 5515. [Abstract] [Full Text]

				J. D. Wallace, R. C. Cuneo, R. Baxter, H. Orskov, N. Keay, C. Pentecost, R. Dall, T. Rosen, J. O. Jorgensen, A. Cittadini, et al. Responses of the Growth Hormone (GH) and Insulin-Like Growth Factor Axis to Exercise, GH Administration, and GH Withdrawal in Trained Adult Males: A Potential Test for GH Abuse in Sport J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3591 - 3601. [Abstract] [Full Text] [PDF]

				S. Ji, R. Guan, S. J. Frank, and J. L. Messina Insulin Inhibits Growth Hormone Signaling via the Growth Hormone Receptor/JAK2/STAT5B Pathway J. Biol. Chem., May 7, 1999; 274(19): 13434 - 13442. [Abstract] [Full Text] [PDF]

				D. Defalque, N. Brandt, J.-M. Ketelslegers, and J.-P. Thissen GH insensitivity induced by endotoxin injection is associated with decreased liver GH receptors Am J Physiol Endocrinol Metab, March 1, 1999; 276(3): E565 - E572. [Abstract] [Full Text] [PDF]