Intralysosomal hydrolysis of thyroglobulin. II. Different fates of poorly and fully iodinated Tg and specific activation by TSH of the degradation of fully iodinated Tg.
Degradations of recently (1 h) iodinated thyroglobulin (Tg) and of Tg iodinated for 48 h (fully iodinated molecule) inside thyroid phagolysosomes have been measured in vitro, at different pH, in basal (lysosomes from normal rats) and stimulated (lysosomes from TSH-treated rats) conditions. In basal conditions, recently iodinated Tg was shown to be preferentially degraded at pH 5 but not at pH 8. Mercaptoethanol (ME) was found to preferentially stimulate the degradation of 48 h-iodinated Tg at pH 5 but not at pH 8. In stimulated conditions and in the presence of ME, no preferential hydrolysis of recently iodinated Tg was observed, whatever the pH. Since the degradation of Tg and its stimulation by ME are known to depend on the mean iodine content of the molecule, it was concluded that: 1) the recently iodinated Tg population contains both poorly and fully iodinated molecules, the degradations of which are faster or similar to that of 48 h-iodinated Tg, respectively, 2) among thyroid phagolysosomes, only those which exhibit a pH-dependent proteolytic activity contain poorly iodinated molecules while others, which are functional at either pH, contain solely fully iodinated molecules (1 and 48 h labelled), 3) reduction of the disulphide bridges of fully iodinated Tg, mediated by ME and probably a lysosomal transhydrogenase, is a prerequisite for its optimal degradation by lysosomal proteinases, 4) in addition, TSH, which preferentially stimulates the degradation of fully iodinated Tg, was concluded to interfere directly upon the intralysosomal hydrolytic process, independently of its effect upon Tg endocytosis. This effect of TSH, similar and additive to that of ME suggests that the hormone might activate a lysosomal transhydrogenase.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007455:Iodine / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*
D008623:Mercaptoethanol; D003994:Bucladesine; D013972:Thyrotropin; D013954:Thyroglobulin; D007455:Iodine; D000242:Cyclic AMP