Rescue from Dwarfism by Thyroid Function Compensation in rdw Rats

Abstract

The rdw rat was initially reported as having hereditary dwarfism caused by pituitary dysfunction. Subsequent studies on the rdw rat, however, have demonstrated that the primary cause of rdw dwarfism is present in the thyroid gland but not in the pituitary gland. The primary cause of rdw rat disorders is a missense mutation of the thyroglobulin (Tg) gene by a one-point mutation.In the present study, we attempted to rescue the dwarfism of the rdw rats using a diet supplemented with thyroid powder (T-powder) and a thyroid graft (T-graft). The infants of the rdw rat were successfully raised to a mature stage body weight, accompanied by elevation of serum growth hormone (GH) and prolactin (PRL), by the T-powder. Furthermore, the T-graft successfully increased the body weight with fertility. The serum GH and PRL levels in the T-graft rdw rat significantly increased. The serum thyroid-stimulating hormone (TSH) levels in the T-graft rdw rat were significantly decreased but were significantly higher than those in the control rat. The GH and PRL mRNA expression in the rdw rat with the T-graft was virtually the same as that of the control, but the TSH β mRNA differed from that of the control rats. Thus, the dwarfism in the rdw rat is rescued by thyroid function compensation, such as that afforded by T-powder and T-graft. Key words: growth, rdw rat, thyroid therapyThe rdw rat (gene symbol: rdw/rdw) was raised by Koto et al. [13] from a closed colony of the Csk: WistarImamichi strain as a variant with pituitary dysfunction. On the basis of an immunohistochemical analysis, the same researchers suggested that the rdw dwarfism was caused by hypoplasia of the pituitary gland. Subsequently, it was revealed that the expressions of mRNA (Received 28 February 2005 / Accepted 1 September 2005 Address corresponding: S. Furudate, Department of Laboratory Animal Science, Japan of growth hormone (GH) and prolactin (PRL) in the rdw rat are drastically decreased [18,21]. In addition, the GH and PRL proteins in the rdw rat are decreased to a level 1/30 to 1/100 of those of a normal rat [17,18].In the rdw rat, the thyroxine (T 4 ) levels in serum are drastically decreased [19,21,23], but the thyroid-stimu-

Impaired Development of Somatotropes, Lactotropes and Thyrotropes in Growth-Retarded (grt) Mice

“…There are fewer GH cells in hyt mice than in wild type 10 . In rdw rats, GH and PRL cells in the anterior lobe are fewer than in normal rats 7 , and again both plasma and mRNA levels of GH and PRL expression in the pituitary are reduced, whereas plasma and mRNA levels of TSH are elevated 13–15 .…”

“…The pituitary of rdw rats is composed of reduced numbers of GH and PRL cells 7 , exhibiting declined levels of GH and PRL mRNA and elevated levels of TSH mRNA. In association with these phenomena, plasma GH and PRL levels are low 12,13 and plasma TSH levels are high 13–15 .…”

Maintaining the thyroid gland in mutant thyroglobulin–induced hypothyroidism requires thyroid cell proliferation that must continue in adulthood

“…7 , A and B ). It has been repeatedly reported that WIC- TG rdw/rdw rats during this period of life (18–40 weeks) do maintain markedly elevated circulating TSH levels ( 23 , 37 , 38 , 39 ), and indeed, we found that older WIC- TG rdw/rdw rats (>30 weeks) exhibited a circulating TSH (32.7 ± 10.7 ng/ml; n = 10) that was 16.6-fold elevated over that of their WT counterparts (1.97 ± 0.11 ng/ml; n = 3). To confirm that the elevated TSH in adult WIC rats should be sufficiently bioactive to stimulate thyroid cell proliferation, we challenged 14-week-old WT WIC rats to induce hypothyroidism, by introducing propylthiouracil (PTU) continuously for 3 weeks before euthanasia and thyroid tissue analysis at 17 weeks.…”

Altered Cerebellum Development and Dopamine Distribution in a Rat Genetic Model with Congenital Hypothyroidism

“…The collected blood samples were allowed to clot and serum was collected after centrifugation at 6000 g . The serum TSH level was determined as described previously by a double‐antibody radioimmunoassay (with reagents provided by the Rat Pituitary Hormone Program, NIDDK, NIH) or by an enzyme‐linked immunosorbent assay (ELISA) (Rodent TSH ELISA Test Kit; Endocrine Technologies Inc., Newark, CA, USA). Total T 3 and T 4 levels were measured using a commercially available ELISA kit (Rodent T 3 ; from Endocrine Technologies, Inc.) and an electrochemiluminescence immunoassay kit (Elecsys T 4 II from Roche Diagnostics Co., Ltd, Mannheim, Germany), respectively.…”