Here's the PNAS abstract:
Proc. Natl. Acad. Sci. USA
Vol. 94, pp. 7239-7244, July 1997
Biochemistry
Requirement of STAT5b for sexual dimorphism of body
growth rates and liver gene expression
Garry B. Udy*, Raewyn P. Towers*, Russell G. Snell*, Richard J. Wilkins, Soo-Hee
Park, Prabha A. Ram, David J. Waxman,,, and Helen W. Davey*,,
* Dairy Science Group, AgResearch, Ruakura, Private Bag 3123, Hamilton, New Zealand;
Department of Biological Sciences, University of Waikato, Hamilton, New Zealand; and Division
of Cell and Molecular Biology, Department of Biology, Boston University, Boston, MA 02215
Communicated by Ronald W. Estabrook, University of Texas Southwestern Medical Center,
Dallas, TX, May 9, 1997 (received for review March 19, 1997)
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. |
