Increased serum inhibin B levels in postmenopausal women with altered thyroid function.

Hyper- and hypothyroidism have significant effects on the female reproductive system. However, little in the way of data is available on the relationship between ovarian paracrine control and thyroid function. This study was aimed at characterising the serum levels of inhibin B in relation to altered thyroid function. Serum inhibin B and FSH levels were measured in 91 women (51 regularly cycling and 40 postmenopausal). The mean serum concentration of inhibin B in euthyroid cycling women (0.025 +/- 0.018 microg/l) was similar to that observed in hyper- and hypothyroid patients (0.022 +/- 0.015 and 0.018 +/- 0.014 microg/l, respectively, p=ns). Inhibin B levels were obviously reduced (-72%) in euthyroid postmenopausal women. In contrast, in hyper- and hypothyroid postmenopausal women, inhibin B levels remained substantially at the premenopausal level. So far, serum inhibin B appeared to be significantly increased in both hyperthyroid patients (0.025 +/- 0.014 microg/l; p<0.0001) and in hypothyroid patients (0.016 +/- 0.006 microg/l; p=0.0006). Altered thyroid function did not affect FSH levels at fertile age. However, a significant decrease of FSH levels was observed in hyper- and hypothyroid (-52% and -43%, respectively) postmenopausal women. Nevertheless, these FSH levels remained in the postmenopausal range. These results indicate that an altered thyroid function affects serum inhibin B levels in postmenopausal women.

Age-related prevalence of platelet-associated immunoglobulins G in nonthrombocytopenic patients with autoimmune thyroid disease and autoimmune polyglandular syndrome.

OBJECTIVE: The prevalence of platelet-associated IgG (paIgG) in nonthrombocytopenic patients with autoimmune thyroid disease (AITD) alone or associated with autoimmune polyglandular syndrome (APS) has been studied. SUBJECTS: A total of 164 individuals were enrolled in this study: 81 patients with AITD alone, 33 patients with APS, and 50 healthy controls. RESULTS: The presence of paIgG was recorded in 41 of 81 patients with AITD (51%) as compared with 2 of 50 control subjects (4%, p < 0.0001). The prevalence of paIgG in patients with APS was higher even when compared with patients with AITD alone (25/33, 76%; p = 0.02). The presence of paIgG was not related to the functional thyroid parameters. The prevalence of paIgG was higher in the older than in the younger patients (75 vs. 47%, p = 0.0037). CONCLUSIONS: The results indicate that the prevalence of paIgG in patients with AITD is higher than previously thought, namely in elderly patients and in patients with APS, and not related to the thyroid function.

Structural organization and chromosomal localization of the human type II deiodinase gene.

OBJECTIVE: The selenoenzyme type 2 iodothyronine 5' deiodinase (DII) catalyzes the conversion of thyroxine into its active form tri-iodothyronine (T3), modulating thyroid hormone homeostasis in a local, tissue-specific manner. The amphibian, rodent and human cDNAs encoding this enzyme have been recently cloned and expressed. At present, little information regarding the genomic structure of mammalian DII is available. DESIGN AND METHODS: The complete structure, including intron-exon junctions, of the human DII (hDII) gene was obtained by long PCR and rapid amplification of cDNA ends (RACE). Chromosomal assignment of the hDII gene was performed by fluorescence in situ hybridization using a highly specific probe. RESULTS AND CONCLUSIONS: Our data demonstrated that hDII is a single copy gene located on chromosome 14, position 14q24.3. The gene spans over 15 kb, and the 7 kb transcript is encoded by three exons of 149 bp, 273 bp and 6.6 kb separated respectively by two 274 bp and 7.4 kb introns. A restriction map of the hDII gene is also reported. These data will help in further studies of the role of DII in the maintenance of peripheral thyroid hormone homeostasis.

Effect of tryptophan on the early tri-iodothyronine uptake in mouse thymocytes.

OBJECTIVE: We have studied the effect of tryptophan on cellular [(125)I]tri-iodothyronine (T3) uptake by mouse thymocytes. MATERIALS AND METHODS: Mouse thymocytes (20 x 10(6 )cells/ml) were suspended in Krebs-Ringer solution buffered by Tris-HCl and incubation (23 degrees C at pH7.45+/-0.6), in the presence or absence of 1mM tryptophan, was started by adding 25 pM [(125)I]T3. At the end of incubation, samples were cooled in ice, centrifuged over a 30% sucrose cushion and the cell-associated radioactivity was measured in the pellet. RESULTS: Tryptophan reduced both the total and the saturable fraction of [(125)I]T3 uptake by 44% (P=0.0009) and 60% (P=0.0006) respectively, following 1 min of incubation. This effect was specific and dose-dependent, being maximal at 5mM concentration (-82%). In contrast, the pre-exposure of cells to tryptophan for up to 2h had no effect on the subsequent uptake of [(125)I]T3, in the absence of tryptophan. The effect of D-tryptophan on saturable T3 uptake was not different from that obtained using the L-stereoisomer. Tryptophan reduced the V(max) of the initial rate of saturable [(125)I]T3 uptake by two-thirds without affecting the apparent K(m) (2.2 nM) of the process, thus indicating the non-competitive nature of the inhibition. In sodium-free medium the saturable [(125)I]T3 uptake was reduced by 43%. The inhibitory effect of tryptophan on [(125)I]T3 uptake was exerted in both the presence and the absence of sodium. In fact, the inhibitory effect of tryptophan on T3 transport was greater and significantly different (P=0.0046) from that obtained by sodium depletion alone. CONCLUSIONS: Tryptophan interferes with both the sodium-dependent and -independent components of [(125)I]T3 uptake by a dose-dependent, non-competitive mechanism which operates in cis-modality at the plasma membrane level of mouse thymocytes.