Modulation of dermal equivalent of hypothalamus-pituitary-adrenal axis in mastocytosis

Jakub Antoniewicz; Bogusław Nedoszytko; Magdalena Lange; Justyna Wierzbicka; Magdalena Górska-Ponikowska; Marek Niedoszytko; Monika Zabłotna; Roman J Nowicki; Michał A Żmijewski

doi:10.5114/ada.2021.107933

Modulation of dermal equivalent of hypothalamus-pituitary-adrenal axis in mastocytosis

Postepy Dermatol Alergol. 2021 Jun;38(3):461-472. doi: 10.5114/ada.2021.107933. Epub 2021 Jul 26.

Authors

Jakub Antoniewicz¹, Bogusław Nedoszytko², Magdalena Lange², Justyna Wierzbicka¹, Magdalena Górska-Ponikowska³, Marek Niedoszytko⁴, Monika Zabłotna², Roman J Nowicki², Michał A Żmijewski¹

Affiliations

¹ Department of Histology, Medical University of Gdansk, Gdansk, Poland.
² Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland.
³ Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
⁴ Department of Pneumatology and Allergology, Medical University of Gdansk, Gdansk, Poland.

Abstract

Introduction: Mastocytosis is a rare disease characterized by abnormal growth and accumulation of tissue mast cells (MC) in one or more organ systems and is classified as being either cutaneous mastocytosis (CM) or systemic mastocytosis (SM). In the pioneer studies of Slominski's group, a fully functional hypothalamic-pituitary-adrenal axis equivalent has been discovered in various tissues, including skin.

Aim: In the present study we investigated potential involvement of hypothalamus-pituitary-adrenal (HPA) cutaneous equivalent in ongoing mastocytosis.

Material and methods: The expression of HPA elements: CRH, UCN1, UCN2, UCN3, CRHR1, POMC, MC1R, MC2R and NR3C1 was assessed for their mRNA level in skin biopsies of adult patients with mastocytosis and healthy donors (n = 16 and 19, respectively), while CRH, UCN1, CRHR1, ACTH and MC1R were selected for immunostaining assay (n = 13 and 7, respectively). The expression of CRH receptor 1 (CRHR1) isomers was investigated by RT-PCR. The ELISA was used for detection of cortisol, CRH, UCN and ACTH in the serum.

Results: The decrease in the expression of HPA element of skin equivalent was observed on both mRNA and protein levels, however quantification of immunohistochemical data was impeded due to melanin in epidermis. Furthermore, we observed infiltration of dermis with HPA elements overexpressing mononuclear cells, which is in the agreement with an in vitro study showing a high expression of HPA elements by mast cells.

Conclusions: Taken together, it was confirmed that the expression elements of HPA was modulated in mastocytosis, thus the potential involvement of general and local stress responses in its pathogenesis should be postulated and further investigated.

Keywords: adrenocorticotropic hormone; corticotrophin-releasing hormone; corticotrophin-releasing hormone receptor; mast cells; mastocytosis; skin hypothalamic-pituitary-adrenal axis.