Da. Stephan et al., THYROID-HORMONE STATUS CORRELATES INVERSELY WITH EXPRESSION OF THE GROWTH-HORMONE RECEPTOR GENE IN RATS IMMEDIATELY AFTER BIRTH, Journal of developmental physiology, 19(6), 1993, pp. 241-246
To investigate the role of thyroid hormone in the expression of the ge
ne encoding the growth hormone receptor (GHR) and growth hormone bindi
ng protein (GHBP), fetal rats were made hypothyroid through the admini
stration of the goitrogen methimazole to the mother. Euthyroidism was
maintained in the mother by concurrent administration of L-thyroxine,
which crosses the placenta poorly. Methimazole and L-thyroxine were co
ntinued in the mothers until weaning. After birth, groups of methimazo
le-treated or control pups were sacrificed immediately and at one, two
, three, four, five, or six weeks after birth. In each group, weight w
as recorded, blood was obtained for measurement of T-4, thyroid Stimul
ating hormone (TSH), and growth hormone (GH), and Liver tissue was obt
ained for quantitation of GHR and GHBP mRNA. The methimazole-treated p
ups were demonstrated to be hypothyroid, with markedly higher TSH and
lower T4 concentrations, until. weaning occurred between weeks three a
nd four, after which they transiently became hyperthyroid at week five
(T-4 = 17 +/- 5 mu g/dL vs. 6 +/- 0.5 mu g/dL for controls) but retur
ned to an euthyroid state at week six. In control pups the relative ab
undance of GHR and GHBP mRNA increased abruptly in week one, and incre
ased three to four fold over the ensuing six weeks. Immediately after
birth, the hypothyroid pups expressed significantly more GHR and GHBP
mRNA than did the controls (P<0.01). The steady state levels of both G
HR and GHBP mRNA then decreased tb the level of the controls by week t
hree, but GHR and GHBP expression was lower for the experimental pups
than for the control pups at week five, coincident with the state of t
ransient hyperthyroidism. Thus, expression of GHR and GHBP mRNA was in
versely related to prevailing thyroid status. Growth hormone concentra
tions were not lower in the methimazole-treated group relative to cont
rols, but the experimental pups had lower weights throughout. We concl
ude that thyroid hormone is involved in the growth regulation of neona
tal rat pups in part by regulating the expression of the mRNA's for GH
R and GHBP.