Autosomal dominant growth hormone (GH) deficiency type II: The del32-71-GH deletion mutant suppresses secretion of wild-type GH

Min S. Lee, Michael P. Wajnrajch, Steve S. Kim, Leslie P. Plotnick, Julie Wang, Joseph M. Gertner, Rudolph L. Leibel, Priscilla S. Dannies

Research output: Contribution to journalArticlepeer-review

Abstract

Familial isolated GH deficiency type II is an autosomal dominant form of short stature, associated in some families with mutations that result in missplicing to produce del32-71-GH, a protein that cannot fold normally. The mechanism by which this mutant suppresses the secretion of wild-type GH encoded by the normal allele is not known. Coexpression of del32-71-GH with wild-type human GH in transient transfections of the neuroendocrine cell lines GH4C1 and AtT20 suppressed accumulation of wild-type GH. The suppression of wild-type GH accumulation by del32-71-GH was a posttranslational effect on wild-type GH caused by decreased stability, rather than decreased synthesis, of wild-type GH. Coexpression of del32-71-GH with human PRL did not suppress accumulation of PRL, indicating that there was not a general suppression of secretory pathway function. Accumulation of del32-71-GH protein was not necessary for the suppression of wild-type GH, because del32-71-GH did not accumulate in the neuroendocrine cell lines in which suppression of accumulation of wild-type GH was observed. Del32-71-GH did accumulate in transfected COS and CHO cells, but did not suppress the accumulation of wild-type GH in these cells. These studies suggest that del32-71-GH may cause GH deficiency in somatotropes of heterozygotes expressing both wild-type and del32-71-GH by decreasing the intracellular stability of wild-type GH.

Original languageEnglish (US)
Pages (from-to)883-890
Number of pages8
JournalEndocrinology
Volume141
Issue number3
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Endocrinology

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