Konrad Patyra1,2, Christoffer Löf1,3, Holger Jaeschke1, Hendrik Undeutsch1,4, Huifei Sophia Zheng5, Sofia Tyystjärvi1,6, Kamila Puławska1, Milena Doroszko1,7, Marcin Chruściel1,8, Britt-Marie Loo9, Riikka Kurkijärvi9, Fu-Ping Zhang1,10,11, Chen-Che Jeff Huang5, Claes Ohlsson12, Andreina Kero2,13, Matti Poutanen1,10, Jorma Toppari1,2, Ralf Paschke14, Nafis Rahman1,15, Ilpo Huhtaniemi16, Jarmo Jääskeläinen17, Jukka Kero2. 1. Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine; Turku, Finland. 2. Department of Pediatrics; Turku, Finland. 3. Molecular Medicine and Genetics of Cancer, Institute of Biomedicine; Turku, Finland. 4. Division of Endocrinology, Diabetes and Metabolism, Joan & Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, New York, USA. 5. Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA. 6. Department of Experimental Neuroimmunology, Klinikum rechst der Isar, Technical University of Munich, Munich, Germany. 7. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 8. Orion Pharma, Turku, Finland. 9. Newborn Screening Centre; Turku, Finland. 10. Turku Center for Disease Modeling; University of Turku, Turku, Finland. 11. GM-Unit of Laboratory Animal Centre and Biomedicum Stem Cell Centre, University of Helsinki, Helsinki, Finland. 12. Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 13. Centre for Population Health Research; Turku University Hospital, Turku, Finland. 14. Cumming School of Medicine, University of Calgary, Calgary, Canada. 15. Department of Reproduction and Gynecology, Medical University of Białystok, Białystok, Poland. 16. Department of Digestion, Metabolism and Reproduction, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom. 17. Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
Abstract
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.
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.
Authors: Shannon L Okada; Jeff L Ellsworth; Diane M Durnam; Harald S Haugen; James L Holloway; Merideth L Kelley; Katherine E Lewis; Hongping Ren; Paul O Sheppard; Harold M Storey; Kimberly S Waggie; Anitra C Wolf; Lena Y Yao; Philippa J Webster Journal: Mol Endocrinol Date: 2005-10-06
Authors: Guoying Yu; Argyris Tzouvelekis; Rong Wang; Jose D Herazo-Maya; Gabriel H Ibarra; Anup Srivastava; Joao Pedro Werneck de Castro; Giuseppe DeIuliis; Farida Ahangari; Tony Woolard; Nachelle Aurelien; Rafael Arrojo E Drigo; Ye Gan; Morven Graham; Xinran Liu; Robert J Homer; Thomas S Scanlan; Praveen Mannam; Patty J Lee; Erica L Herzog; Antonio C Bianco; Naftali Kaminski Journal: Nat Med Date: 2017-12-04 Impact factor: 53.440