Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function.

Autor: Patyra K; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Department of Pediatrics; Turku, Finland., Löf C; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Molecular Medicine and Genetics of Cancer, Institute of Biomedicine; Turku, Finland., Jaeschke H; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland., Undeutsch H; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Division of Endocrinology, Diabetes and Metabolism, Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA., Zheng HS; Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA., Tyystjärvi S; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Department of Experimental Neuroimmunology, Klinikum rechst der Isar, Technical University of Munich, Munich, Germany., Puławska K; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland., Doroszko M; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Chruściel M; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Orion Pharma, Turku, Finland., Loo BM; Newborn Screening Centre; Turku, Finland., Kurkijärvi R; Newborn Screening Centre; Turku, Finland., Zhang FP; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Turku Center for Disease Modeling; University of Turku, Turku, Finland.; GM-Unit of Laboratory Animal Centre and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland., Huang CJ; Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA., Ohlsson C; Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Kero A; Department of Pediatrics; Turku, Finland.; Centre for Population Health Research; Turku University Hospital, Turku, Finland., Poutanen M; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Turku Center for Disease Modeling; University of Turku, Turku, Finland., Toppari J; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Department of Pediatrics; Turku, Finland., Paschke R; Cumming School of Medicine, University of Calgary, Calgary, Canada., Rahman N; Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland.; Department of Reproduction and Gynecology, Medical University of Białystok, Białystok, Poland., Huhtaniemi I; Department of Digestion, Metabolism and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom., Jääskeläinen J; Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland., Kero J; Department of Pediatrics; Turku, Finland.
Jazyk: angličtina
Zdroj: Thyroid : official journal of the American Thyroid Association [Thyroid] 2022 Apr; Vol. 32 (4), pp. 459-471.
DOI: 10.1089/thy.2021.0535
Abstrakt: Background: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans. Methods: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA). Results: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA. Conclusions: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.
Databáze: MEDLINE