{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:02:55Z","timestamp":1791846175704,"version":"4.3.4"},"reference-count":160,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local\/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the \u201cendocrine lung\u201d. This narrative review summarizes current evidence on the endocrine\u2013pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing\u2019s syndrome, hypoventilation in hypothyroidism, restrictive \u201cdiabetic lung\u201d, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH\/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic\u2013pituitary\u2013adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions.<\/jats:p>","DOI":"10.3390\/jcm14196985","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T10:22:32Z","timestamp":1759400552000},"page":"6985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Endocrinology and the Lung: Exploring the Bidirectional Axis and Future Directions"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1985","authenticated-orcid":false,"given":"Pedro","family":"Iglesias","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, C. Joaqu\u00edn Rodrigo, 1, 28222 Majadahonda, Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Puerta de Hierro Segovia de Arana, 28222 Majadahonda, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1210\/jc.2005-0556","article-title":"Expression of Glucocorticoid, Retinoid, and Thyroid Hormone Receptors during Human Lung Development","volume":"90","author":"Rajatapiti","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1677\/joe.1.06530","article-title":"Developmental Regulation of the Lung in Preparation for Life after Birth: Hormonal and Nutritional Manipulation of Local Glucocorticoid Action and Uncoupling Protein-2","volume":"188","author":"Gnanalingham","year":"2006","journal-title":"J. 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