Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas

Baur, A; Buchfelder, Michael; Köhrle, Josef

doi:10.1530/eje.0.1470263

Cited by 42 publications

(31 citation statements)

References 34 publications

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“…4). The expression of the TSH receptor reported earlier in MHC-class II cells (40) and the increase in D2 activity that has been observed in TSH-producing tumors (41) suggests that D2 expression in the anterior pituitary can be influenced directly by TSH. This is further supported by a dose-dependent increase of D2 mRNA by TSH, which has been reported in human thyroid cells and the presence of a cAMP response element in the D2 promoter (42).…”

Section: Discussionmentioning

confidence: 65%

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Alkemade¹,

Friesema²,

Kuiper³

et al. 2006

eur j endocrinol

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Objective: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry. Results: We found TR isoforms to be expressed most prominently in gonadotropes and -although to a lesser extent -in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression. Conclusions: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T 4 ).European Journal of Endocrinology 154 491-500

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Section: Discussionmentioning

confidence: 65%

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Alkemade¹,

Friesema²,

Kuiper³

et al. 2006

eur j endocrinol

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“…Further examinations at different time points during adulthood or after prolonged Orx are needed to distinguish between these two hypotheses. In addition, androgen-modulated paracrine regulation between different pituitary cell types, which express distinct levels of DIO enzymes and/or TH transporters, might influence the fine tuning of anterior pituitary feedback regulation of the HPT axis with increasing age (Baur et al 2002, Denef 2008, Liao et al 2011.…”

Section: Discussionmentioning

confidence: 99%

“…Three DIO isoenzymes have been identified in mammals (Bianco et al 2002) so far: type 1 (DIO1), type 2 (DIO2), and type 3 (DIO3). Their expression and activity are highly development and tissue specific and depend on numerous hormonal, environmental, and nutritional factors (Köhrle 2002).…”

Section: Introductionmentioning

confidence: 99%

Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity

Šošić‐Jurjević

Filipović

Renko

et al. 2012

Journal of Endocrinology

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Endogenous androgens are involved in regulation of thyroid function and metabolism of thyroid hormones. As serum testosterone level progressively declines with age, this regulation may change. We tested how androgen deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery, animals were decapitated. Thyroids were used for histomorphometric and ultrastructural examinations and together with livers and pituitaries for real-time quantitative PCR and deiodinase (DIO) activity measurements. Serum testosterone, TSH, L-thyroxine (T 4 ), and cholesterol (Chol) levels were determined. As expected, middle-aged control rats had lower (P!0 . 05) testosterone and T 4 compared with 3-month-old males. In the Orx middle-aged group, we detected diminished serum testosterone (P!0 . 05), no change in TSH and T 4 levels, and higher Chol level (P!0 . 05), in comparison with age-matched controls. Histomorphometric analysis of thyroid tissue revealed decreased relative volume densities of follicles and colloid (P!0 . 05). Relevant gene expressions and DIO1 enzyme activity were not changed in the thyroids of Orx rats. Liver Dio1 gene expression and DIO1 activity were decreased (P!0 . 05) in comparison with the control values. Pituitary levels of TSHb, Dio1, and Dio2 mRNAs did not change, while DIO2 activity decreased (P!0 . 05). In conclusion, orchidectomy of middle-aged rats affected thyroid structure with no effect on serum T 4 and TSH. However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate compensatoryadaptive changes in local T 3 production.

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“…The anterior pituitary contains D1 and D2, which play a role in T 3 production and pituitary feedback (16,17). The effects of IL-1b, IL-6 and TNFa on pituitary D1 and D2 activity in reaggregates of rat anterior pituitaries were studied, and in these reaggregates, IL-1b (dose-dependently) and TNFa increased D2 activity (18).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-18, a proinflammatory cytokine, contributes to the pathogenesis of non-thyroidal illness mainly via the central part of the hypothalamus-pituitary-thyroid axis

Boelen

Kwakkel

Schiphorst

et al. 2004

European Journal of Endocrinology

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Objective: Proinflammatory cytokines are involved in the pathogenesis of non-thyroidal illness (NTI), as shown by studies with IL-6 2/2 and IL-12 2/2 mice. Interleukin (IL)-6 changes peripheral thyroid hormone metabolism, and IL-12 seems to be involved in the regulation of the central part of the hypothalamic-pituitary-thyroid (HPT) axis during illness. IL-18 is a proinflammatory cytokine which shares important biological properties with IL-12, such as interferon (IFN)-g-inducing activity. Design: By studying the changes in the HPT-axis during bacterial lipopolysaccharide (LPS)-induced illness in IL-18 2/2 , IFNgR 2/2 and wild-type (WT) mice, we wanted to unravel the putative role of IL-18 and IFNg in the pathogenesis of NTI. Results: LPS induced a decrease in pituitary type 1 deiodinase (D1) activity (P , 0.05, ANOVA) in WT mice, but not in IL-18 2/2 mice, while the decrease in D2 activity was similar in both strains. LPS decreased serum thyroid hormone levels and liver D1 mRNA within 24 h similarly in IL-18 2/2 , and WT mice. The expression of IL-1, IL-6 and IFNg mRNA expression was significantly lower in IL-18 2/2 mice than in WT, while IL-12 mRNA expression was similar. IFNgR 2/2 mice had higher basal D1 activity in the pituitary than WT mice (P , 0.05); LPS induced a decrease of D2, but not of D1, activity in the pituitary which was similar in both strains. In the liver, the LPS-induced increase in cytokine expression was not different between IFNgR 2/2 mice and WT mice, and the decrease in serum T 3 and T 4 levels and hepatic D1 mRNA was also similar. Conclusions: The relative decrease in serum T 3 and T 4 and liver D1 mRNA in response to LPS is similar in IL-18 2/2 , IFNgR 2/2 and WT mice despite significant changes in hepatic cytokine induction. However, the LPS-induced decrease in D1 activity in the pituitary of WT mice is absent in IL-18 2/2 mice; in contrast, LPS did not decrease pituitary D1 activity in the IFNgR 2/2 mice or their WT, which might be due to the genetic background of the mice. Our results suggest that IL-18 is also involved in the regulation of the central part of the HPT axis during illness.

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Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas

Cited by 42 publications

References 34 publications

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Novel neuroanatomical pathways for thyroid hormone action in the human anterior pituitary

Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity

Interleukin-18, a proinflammatory cytokine, contributes to the pathogenesis of non-thyroidal illness mainly via the central part of the hypothalamus-pituitary-thyroid axis

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