Effect of neonatal hyperthyroidism on GH gene expression reprogramming and physiological repercussions in rat adulthood.
The neonatal period (NP) is a critical phase of the development in which the expression pattern of most genes is established. Thyroid hormones (TH) play a key role in this process and, alterations in its availability in the NP may lead to different patterns of gene expression, which might reflect in the permanent expression of several genes in the adulthood. GH gene expression in the pituitary is greatly dependent on TH in the early postnatal life; thus, modifications of thyroid state in NP might lead to alterations in GH gene expression as well as to physiological repercussions in the adult life. This study aimed to investigate this possibility by means of the induction of a neonatal hyperthyroidism in rats (4 mug of 3,5,3'-triiodo-l-thyronine (T3)/100 g body weight, s.c.) for 5, 15 or 30 days, and further evaluation of GH gene expression, as well as its physiological consequences in adult rats subjected to a transient hyperthyroidism in the first 30 days of life. GH mRNA level was shown to be increased in T3-treated rats for 5 days; when the treatment was extended to 15 or 30 days, the GH mRNA levels were similar to the control group. Moreover, rats treated with T3 for 30 days and killed when 90 days old, i.e., 60 days at the end of the T3 treatment, showed decreased GH mRNA content, body weight, bone mineral density, and lean body mass.


CONCLUSIONS
(1) T3 effects on GH gene expression depend on the period of life in which the hyperthyroidism is set and on the length of T3 treatment in the NP and (2) transient neonatal hyperthyroidism leads to a lower GH mRNA expression in adult life accompanied by physiological repercussions indicative of GH deficiency.
de Picoli Souza
Kely
K
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, SP, Brazil.
Silva
Francemilson Goulart da
FG
Nunes
Maria Tereza
MT
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D001823:Body Composition; D001835:Body Weight; D015519:Bone Density; D005260:Female; D018507:Gene Expression Regulation, Developmental; D013006:Growth Hormone / Q000172:deficiency / Q000235:genetics*; D006980:Hyperthyroidism / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine
D012333:RNA, Messenger; D014284:Triiodothyronine; D013006:Growth Hormone