Congenital Goitre in Sheep: Isolation of the Iodoproteins Which Replace Thyroglobulin

Abstract

Immunological and chromatographic studies of proteins from the congenital goitre of South Australian Merino sheep revealed that normal thyroglobulin is absent from the thyroid glands of these sheep. However, a thyroglobulin-immunoreactive iodoprotein was isolated by affinity chromatography on agarose gel to which antibody against thyroglobulin had been covalently bound. Sucrose-gradient ultracentrifugation indicated that this iodoprotein had a sedimentation coefficient of 8S and a molecular weight of approximately 175000. This iodoprotein is therefore about one quarter the size of normal thyroglobulin (19S; 660000) and is similar in size to the subunit of thyroglobulin (3-8S; 165000) although this has usually been described as non-iodinated except when derived by reductive fission. In addition the goitre extract contained iodoproteins which had the immunological properties of serum albumin and immunoglobulin G. Determination of the iodine and iodoamino acid content of the hydrolysed iodoproteins revealed that they contained iodothyronines which were able to contribute to the production of thyroid hormones although the total iodothyronine content of the goitrous gland was less than that of the normal sheep thyroid gland.

Inherited primary hypothyroidism with thyrotrophin resistance in Japanese cats

“…The development of goiter in hypothyroidism may be due to a defect in thyroid hormone and thyroglobulin syntheses (Dolling & Good, 1976;Silva, Stantelices, Kishihara & Schneider, 1984;Ricketts, Pohl, de Martynoff et al 1985 ). However, it is also known that there is nongoitrous hypothyroidism which is unresponsive to TSH.…”

Molecular advances in thyroglobulin disorders

“…Tg synthesis defects have been described not only in men, but also in cattle [167][168][169][170][171][172][173], goats [174][175][176][177], sheep [178][179][180][181][182][183], mouse [184][185][186], rats [187][188][189][190] and Bongo antelopes [191]. Hypothyroidism linked to Tg mutations have been reported in Afrikander cattle (p.R697X) [192][193][194][195], Dutch goats (p.Y296X) [196][197][198], cog/cog mouse (p.L2263P) [199] and rdw rats (p.G2300R) [200][201][202] (Table 4).…”

Hereditary Congenital Goitre With Thyroglobulin Deficiency Causing Hypothyroidism

“…Several thyroid disorders are known in man and animals in which the amount of Tg is reduced or in which abnormal Tg is found and often abnormal iodoproteins have been identified (Van Voorthuizen, 1978;. Until now three animal models of Tg disorders have been described in the literature: in cattle (Van Jaarsfeld et al, 1972;Sinadinovic et al, 1982), Merino sheep (Rac et al, 1968Falconer et al, 1970;Dolling & Good, 1975) and goats (De Vijlder et al, 1978;Van Voorthuizen, 1978).…”

“…Evidence has been presented in the past (Van Voorthuizen, 1978) that Tg'is synthesized on large polysomes bound to the endoplasmic reticulum of the thyroid cell and then transported via the Golgi apparatus to the apical cell membrane where iodination of the tyrosil residues takes place . Several thyroid disorders have been reported in man (Michel et al, 1964;Mouriz et al, 1969;Andreoli et al, 1970;Lissitzky et al, 1973;Savoie et al, 1973;Riesco et al, 1974;Monaco et al, 1974;Wagar et al, 1976) and animals (Rae et al, 1968;Falconer er al., 1970;Van Jaarsveld et al, 1972;De Vijlder et al, 1978;Dolling et al, 1975;Sinadinovic et ul., 1982) in which the amount of thyroid Tg is reduced, absent or an abnormal Tg is found. Although the exact nature of the underlying defect in human beings remains unknown it was suggested that lack of Tg in congenital goitre is due to a defect in Tg messenger RNA which leads to aberrant processing and transport of Tg from its site of synthesis to the endoplasmic reticulum (Van Voorthuizen et al, 1978).…”