Biology Reference
In-Depth Information
associated with its tissue-specific metamorphic outcome, and functions ascribed to
many of these genes correspond to histological changes induced by TH. Also, the large
number of transcription factors identified in microarrays is consistent with the molecular
mechanisms of TH action. On the other hand, microarray analysis has also revealed
interesting findings not predicted from previous morphological or molecular studies.
Furthermore, endocrine disruption studies identified candidate biomarkers for TH dis-
ruption, and the mechanisms of action of several endocrine disrupting chemicals have
been examined. The microarray studies described here have produced a wealth of data
on gene expression that requires further functional studies to elucidate the roles of
these genes in development and endocrine disruption.
1. INTRODUCTION
All vertebrates require thyroid hormone (TH) for normal development,
especially for the central nervous system (
Howdeshell, 2002
). The actions of
hormones on development are particularly striking in frogs, where metamor-
phosis represents one of the most remarkable sets of hormone-dependent
changes known among chordates (
Just, Kraus-Just, & Check, 1981
). The role
of hormones in development is more easily studied in free-living tadpoles
compared to uterus-enclosed mammalian embryos/fetuses because interpre-
tations of hormonal manipulations in developingmammals are confounded by
effects on the mother (
Tata, 1993
). Thus, the exquisite dependence of frog
metamorphosis on TH and ease of analysis compared to mammals lends itself
not only to studies of normal hormone-dependent development but also to
studies of disturbed development due to endocrine disrupting chemicals.
Metamorphosis transforms the tadpole from one morphotype to another,
involving extensive changes in morphology, biochemistry, and physiology
(
Dodd & Dodd, 1976
). For example, tadpoles possess tails for swimming,
their intestine is adapted for an herbivorous diet, and brain and skin are larval
in character. During metamorphosis, the tail is completely resorbed, intes-
tine, brain, and skin undergo extensive remodeling, and limbs grow out. In
addition, the liver changes from ammonotelic to ureotelic metabolism of ni-
trogenous waste, and blood cells transform from larval to adult versions. TH
is responsible for initiating all of these events of metamorphosis. If tadpoles
are treated via surgical or chemical thyroidectomy such that they cannot
make TH, they grow larger in size as a tadpole but do not undergo meta-
morphic changes. Conversely, TH added to the rearing water of
premetamorphic tadpoles initiates all of the metamorphic changes that
would have occurred later.
