Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse

1985 ◽  
Vol 63 (9) ◽  
pp. 1151-1154
Author(s):  
Peter Walker

Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 μg of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay. SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P < 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P < 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 μg/d) of adult mice, SMG weight in NH mice increased significantly (P < 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P < 0.01). However, the magnitude of the increase was markedly obtunded in adult NH mice. These observations indicate that thyroid hormones precociously and exponentially increase SMG EGF content and concentration in neonatal mice. The marked increases strongly suggest thyroid hormone mediated synthesis of EGF and acceleration of maturation of gene expression for EGF synthesis. In addition, NH appears to modify thyroid hormone regulation of gene expression for EGF synthesis in adult mice.

Endocrinology ◽  
1993 ◽  
Vol 132 (1) ◽  
pp. 121-125 ◽  
Author(s):  
M Fujieda ◽  
Y Murata ◽  
H Hayashi ◽  
F Kambe ◽  
N Matsui ◽  
...  

Endocrinology ◽  
1986 ◽  
Vol 119 (3) ◽  
pp. 1382-1387 ◽  
Author(s):  
RUTH M. GUBITS ◽  
PHYLLIS A. SHAW ◽  
EDWARD W. GRESIK ◽  
ANDREA ONETTI-MUDA ◽  
TIBOR BARKA

1989 ◽  
Vol 121 (2) ◽  
pp. 269-275 ◽  
Author(s):  
S. Kasayama ◽  
M. Yoshimura ◽  
T. Oka

ABSTRACT The effects of androgen and thyroid hormones on epidermal growth factor (EGF) synthesis in the submandibular gland and on plasma EGF concentrations in mice were examined. Testosterone propionate was administered alone or in combination with l-thyroxine (T4) to female mice for 2 weeks. The submandibular EGF concentrations were increased by the administration of testosterone propionate in a dose-dependent fashion; the maximal increase, 20-fold, being produced by a dose of 2 mg every other day. The EGF levels were increased sevenfold by T4, which also enhanced the stimulatory effect of suboptimal doses of testosterone propionate. Cyproterone acetate, an anti-androgen, inhibited the testosterone propionate-induced increase, but not the T4-induced increase. Plasma EGF concentrations were raised by testosterone propionate but not by T4. Both hormones stimulated the accumulation of 4·7 kb preproEGF mRNA in the submandibular gland, which occurred almost in a parallel manner with the increase in submandibular EGF concentrations. These results suggest that EGF synthesis in the submandibular gland is regulated by alterations in the level of its mRNA by thyroid hormones and androgen, and that the rise in plasma EGF concentrations is under the influence of androgen but not of thyroid hormones. Journal of Endocrinology (1989) 121, 269–275


1987 ◽  
Vol 29 (2) ◽  
pp. 215-220
Author(s):  
Masahiko Hiramatsu ◽  
Akinao Sato ◽  
Masanori Kashimata ◽  
Naoyuki Minami ◽  
Naomi Minami

1986 ◽  
Vol 64 (4) ◽  
pp. 290-296 ◽  
Author(s):  
Peter Walker

Thyroid hormones are known to modulate the concentrations of epidermal growth factor (EGF) in the mouse submandibular gland (SMG); this action is presumably mediated by the nuclear triiodothyronine receptor. To test the hypothesis that thyroid hormones act to increase SMG EGF concentrations by increasing the number of poly(A)+-specific mRNA, poly(A)+ RNA was isolated from SMGs of neonatal mice which had been treated daily from birth through to 21 days of age with thyroxine (T4, 0.4 μg/g body weight). Poly(A)+ RNA also was extracted from SMGs of intact 21-day-old mice which had received vehicle alone. No significant differences in total nucleic acid, total RNA, or poly(A)+ RNA yields were noted between the two groups of animals. The isolated poly(A)+ RNAs from T4-treated and control mice were translated in an in vitro wheat germ system. Although no significant differences in efficiency of [35S]cysteine incorporation into trichloracetic acid precipitable material were noted between the two poly(A)+ RNA preparations, a significantly greater proportion of radioactivity was immunoprecipitable by anti-EGF antiserum in the translation medium derived from T4-treated mice (17.2 ± 0.9%, mean ± SEM) than in that of control mice (7.3 ± 0.5%, P < 0.001). Polyacrylamide gel electrophoresis of the immunoprecipitates (IMMP) revealed the presence of three radioactive bands with apparent relative masses (Mrs) of 12 000, 9000, and 6000. The latter species comigrated with purified EGF, [125I]EGF, and an IMMP of a SMG extract. The translation product IMMPs following polyacrylamide gel electrophoresis were iodinated and digested with α-chymotrypsin. Autoradiograms, following high-voltage electrophoresis and ascending chromatography on thin-layer cellulose, showed a marked similarity of the peptide maps of purified EGF, the IMMP of a SMG extract, and the translation product IMMPs. Furthermore, the peptide maps of the Mr 12 000, 9000, and 6000 IMMPs were highly concordant, suggesting that the Mr 12 000 and 9000 species are structurally related to the Mr 6000 EGF species. These observations support the hypothesis that thyroid hormones increase SMG EGF concentrations by increasing the number of poly(A)+ RNA species coding for EGF.


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