Biology Reference
In-Depth Information
2.1.1 Feedback regulation of TSH
Negative feedback by TH on the hypothalamus and pituitary plays a central
role in thyroid homeostasis in all adult vertebrates that have been studied
including frogs (
Fig. 7.1
;
Jacobs & Kuhn, 1992; Kaneko et al., 2005
).
The discovery of a sustained rise in TSH production and thyroid activity
during tadpole metamorphosis led
Etkin (1968
) to hypothesize that negative
feedback on pituitary TSH does not develop until metamorphic climax.
Huang et al. (2001)
proposed that the onset of negative feedback at meta-
morphic climax was coincident with the expression of
Dio2
in the tadpole
pituitary. However, many investigators have found that negative feedback
by TH on TSH is active in the premetamorphic and early prometamorphic
tadpole. For example, treatment of premetamorphic tadpoles with goitro-
gens caused enlargement of the thyroid gland and degranulation of pituitary
thyrotropes, while replacement with T
4
reversed the effects, suggesting that
negative feedback was functional in the premetamorphic tadpole (
Dodd &
Dodd, 1976; Goos, 1968, 1978; Goos, Deknecht, & Devries, 1968
). Fur-
ther, goitrogen treatment of premetamorphic tadpoles caused a dramatic el-
evation in
tsh
b
mRNA (
Buckbinder & Brown, 1993; Huang et al., 2001
).
Physiological concentrations of T
4
or T
3
can act directly on pituitary ex-
plants of
X. laevis
tadpoles throughout metamorphosis to suppress
tsh
b
mRNA expression and TSH secretion (
Manzon & Denver, 2004;
Sternberg et al., 2011
). Pituitary sensitivity to negative feedback by TH
may decline slightly during late prometamorphosis and metamorphic cli-
max, perhaps due to the upregulation of pituitary
Dio3
at this time
(
Manzon & Denver, 2004; Sternberg et al., 2011
).
Kaneko et al. (2005)
found that CRF-induced TSH release by bullfrog primary pituitary cells
was suppressed by T
3
throughout metamorphosis. Taken together, these
findings support that negative feedback at the level of the pituitary is active
in the premetamorphic and early prometamorphic tadpole, which does not
support Etkin's hypothesis and contradicts
Huang et al. (2001)
.
Deiodinase type 2 plays an important role in TH-negative feedback on
TSH in mammals (
Schneider et al., 2001; St Germain, Hernandez,
Schneider, & Galton, 2005
). The
Dio2
gene is expressed in the tadpole from
early prometamorphosis and shows a progressive increase during metamor-
phosis, reaching a maximum by NF stage 59 (
Manzon & Denver, 2004
).
This supports the findings discussed above that T
4
, likely through conversion
to T
3
, exerts negative feedback on TSH throughout tadpole metamorphosis.
The downregulation of TSH expression by T
4
suggests that 5
0
-deiodinase
activity is either present in the pituitary throughout prometamorphosis or
