A potential impact of SARS-CoV-2 on pituitary glands and pituitary neuroendocrine tumors

  • Endocrine. 2021 May;72(2):340-348. doi: 10.1007/s12020-021-02697-y.
Wei Ting Gu   #  1 ,  Fen Zhou   #  2 ,  Wan Qun Xie   #  1 ,  Shuo Wang  2 ,  Hong Yao  1 ,  Yan Ting Liu  1 ,  Ling Gao  3 ,  Zhe Bao Wu  4
Affiliations
  • 1. Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
  • 2. Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, 430060, Wuhan, China.
  • 3. Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, 430060, Wuhan, China. [email protected].
  • 4. Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 33786714 DOI: 10.1007/s12020-021-02697-y
Abstract

Introduction: Angiotensin-converting enzyme 2 (ACE2) is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effects of SARS-CoV-2 on normal pituitary glands function or pituitary neuroendocrine tumors (PitNETs) have not yet been elucidated. Thus, the present study aimed to investigate the potential risks of SARS-CoV-2 Infection on the impairment of pituitary glands and the development of PitNETs.

Methods: PitNETs tissues were obtained from 114 patients, and normal pituitary gland tissues were obtained from the autopsy. The mRNA levels of ACE2 and angiotensin II receptor type 1 (AGTR1) were examined by quantitative Real-Time PCR. Immunohistochemical staining was performed for ACE2 in 69 PitNETs and 3 normal pituitary glands. The primary tumor cells and pituitary cell lines (MMQ, GH3 and AtT-20/D16v-F2) were treated with diminazene aceturate (DIZE), an ACE2 agonist, with various dose regimens. The pituitary Hormones between 43 patients with SARS-CoV-2 Infection were compared with 45 healthy controls.

Results: Pituitary glands and the majority of PitNET tissues showed low/negative ACE2 expression at both the mRNA and protein levels, while AGTR1 showed high expression in normal pituitary and corticotroph adenomas. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum adrenocorticotropic hormone (ACTH) was significantly increased in COVID-19 patients compared to normal controls (p < 0.001), but was dramatically decreased in critical cases compared to non-critical patients (p = 0.003).

Conclusions: This study revealed a potential impact of SARS-CoV-2 Infection on corticotroph cells and adenomas.

Keywords
Angiotensin II receptor type 1; Angiotensin-converting enzyme 2; Pituitary gland; Pituitary neuroendocrine tumors; Severe acute respiratory syndrome coronavirus 2.
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