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developmental
endocrinology branch
Carolyn Bondy, MD,
Chief The mission of the Developmental Endocrinology
Branch (DEB) is to investigate diseases that affect the processes of human growth,
development, and reproduction. The branch has focused on genetic as well as
on classical endocrine approaches to short stature, childhood obesity,
endocrine tumors, Turner syndrome, and premature ovarian failure. Senior
staff members are clinicians involved in patient care and training of
clinical fellows, with weekly ward rounds and clinic conferences. From
careful study of patients at the bedside, DEB investigators develop insights
that lead to new “basic” approaches to elucidation of the
molecular mechanisms of these disorders and to the development of new
diagnostic and therapeutic approaches. Thus, the DEB’s
multidisciplinary, integrative program combines direct patient care research
and clinically oriented basic research strategies in order to translate basic
biomedical research findings into practical bedside applications. Greti
Aguilera’s group, the Section
on Endocrine Physiology, focuses on the molecular mechanisms controlling
neuroendocrine components of the stress response. They demonstrated that cAMP
stimulates CRH expression at transcriptional and post-transcriptional levels
and contributes to limiting the duration of the transcriptional response
through the production of cAMP-inducible early repressor (ICER). They also
identified novel mechanisms by which vasopressin receptors activate the EGF
receptor and MAP kinase pathway, a mechanism that in turn induces V1b
receptor transcription. Jeffrey Baron’s
laboratory, the Unit on Growth and
Development, had previously shown that longitudinal bone growth slows
with age and eventually stops because growth plate chondrocytes undergo
replicative senescence. Recently, the laboratory demonstrated that the
mechanisms responsible for this replicative senescence in vivo are distinct from those causing replicative senescence in vitro and may involve loss of DNA
methylation and associated epigenetic modifications. Carolyn Bondy
heads the Section on Growth and
Metabolism, the Section on
Women’s Health Research, and
the Unit on Turner’s Syndrome. She
and her coworkers have shown that young healthy women with monosomy X or
Turner's syndrome have higher blood pressure and a distinctly more
atherogenic lipid profile than age- and body fat–matched women with
karyotypically normal premature ovarian failure, suggesting that a normal
second X chromosome may protect women from atherosclerotic vascular disease
through beneficial effects on blood pressure and lipid metabolism. In
addition, Bondy’s team detected distinctive and novel cardiac
conduction and repolarization abnormalities in Turner syndrome that provide
new insight into the congenital heart defects associated with this disorder. Lawrence Nelson’s
unit, the Unit on Gynecologic
Endocrinology, has elucidated the multifaceted nature of spontaneous
premature ovarian failure by demonstrating that young women with this
condition have significantly more symptoms of dry eye and eye surface damage
than age-matched controls. In the laboratory, Nelson’s group defined
the developmental expression and subcellular localization of mouse MATER, an
antigen in a mouse model of autoimmune ovarian failure and an oocyte-specific
protein essential for early development. Jack Yanovski’s
group, the Unit on Growth and Obesity,
showed that polymorphisms in the melanocortin 3 receptor partially inactivate
its function and are highly associated with pediatric obesity, particularly
in African Americans. The data are the first to demonstrate the importance of
this receptor for body weight regulation in humans. A second line of
investigation found that, among children at risk for adult obesity, those
reporting binge eating behaviors had a significantly greater risk of abnormal
weight gain over a three-year observation period than children who did not
report such behaviors. The novel data lay the groundwork for developing
specific, etiology-based strategies for the prevention and treatment of
pediatric obesity. Constantine Stratakis’s group, the Section on Endocrinology and Genetics, showed that mouse models
of PRKAR1A-downregulation replicate many of the findings of the human disease
known as the Carney complex. DNA array studies have defined novel molecular
pathways involved in adrenocortical tumorigenesis, with additional clinical
and molecular studies identifying a new type of micronodular bilateral
hyperplasia in infants and young children. |