DOI: 10.1073/pnas.94.14.7239. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression

Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression

10.1073/pnas.94.14.7239

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The signal transducer and activator of transcription, STAT5b, has been implicated in signal transduction pathways for a number of cytokines and growth factors, including growth hormone (GH). Pulsatile but not continuous GH exposure activates liver STAT5b by tyrosine phosphorylation, leading to dimerization, nuclear translocation, and transcriptional activation of the STAT, which is proposed to play a key role in regulating the sexual dimorphism of liver gene expression induced by pulsatile plasma GH. We have evaluated the importance of STAT5b for the physiological effects of GH pulses using a mouse gene knockout model. STAT5b gene disruption led to a major loss of multiple, sexually differentiated responses associated with the sexually dimorphic pattern of pituitary GH secretion. Male-characteristic body growth rates and male-specific liver gene expression were decreased to wild-type female levels in STAT5b −/− males, while female-predominant liver gene products were increased to a level intermediate between wild-type male and female levels. Although these responses are similar to those observed in GH-deficient Little mice, STAT5b −/− mice are not GH-deficient, suggesting that they may be GH pulse-resistant. Indeed, the dwarfism, elevated plasma GH, low plasma insulin-like growth factor I, and development of obesity seen in STAT5b −/− mice are all characteristics of Laron-type dwarfism, a human GH-resistance disease generally associated with a defective GH receptor. The requirement of STAT5b to maintain sexual dimorphism of body growth rates and liver gene expression suggests that STAT5b may be the major, if not the sole, STAT protein that mediates the sexually dimorphic effects of GH pulses in liver and perhaps other target tissues. STAT5b thus has unique physiological functions for which, surprisingly, the highly homologous STAT5a is unable to substitute.

Bibliography

Udy, G. B., Towers, R. P., Snell, R. G., Wilkins, R. J., Park, S.-H., Ram, P. A., Waxman, D. J., & Davey, H. W. (1997). Requirement of STAT5b for sexual dimorphism of body growth rates and liver geneâexpression. Proceedings of the National Academy of Sciences, 94(14), 7239â7244.

Authors 8

Garry B. Udy (first)
Raewyn P. Towers (additional)
Russell G. Snell (additional)
Richard J. Wilkins (additional)
Soo-Hee Park (additional)
Prabha A. Ram (additional)
David J. Waxman (additional)
Helen W. Davey (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:28 p.m.)
Indexed	2 days, 18 hours ago (Aug. 29, 2025, 6:48 a.m.)
Issued	28 years, 1 month ago (July 8, 1997)
Published	28 years, 1 month ago (July 8, 1997)
Published Online	28 years, 1 month ago (July 8, 1997)
Published Print	28 years, 1 month ago (July 8, 1997)

Funders 0

None

BibTeX

@article{Udy_1997, title={Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.14.7239}, DOI={10.1073/pnas.94.14.7239}, number={14}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Udy, Garry B. and Towers, Raewyn P. and Snell, Russell G. and Wilkins, Richard J. and Park, Soo-Hee and Ram, Prabha A. and Waxman, David J. and Davey, Helen W.}, year={1997}, month=jul, pages={7239–7244} }

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