Progress in salivary glands: Endocrine glands with immune functions.

The production and secretion of saliva is an essential function of the salivary glands. Saliva is a complicated liquid with different functions, including moistening, digestion, mineralization, lubrication, and mucosal protection. This review focuses on the mechanism and neural regulation of salivary secretion, and saliva is secreted in response to various stimuli, including odor, taste, vision, and mastication. The chemical and physical properties of saliva change dynamically during physiological and pathophysiological processes. Moreover, the central nervous system modulates salivary secretion and function via various neurotransmitters and neuroreceptors. Smell, vision, and taste have been investigated for the connection between salivation and brain function. The immune and endocrine functions of the salivary glands have been explored recently. Salivary glands play an essential role in innate and adaptive immunity and protection. Various immune cells such as B cells, T cells, macrophages, and dendritic cells, as well as immunoglobins like IgA and IgG have been found in salivary glands. Evidence supports the synthesis of corticosterone, testosterone, and melatonin in salivary glands. Saliva contains many potential biomarkers derived from epithelial cells, gingival crevicular fluid, and serum. High level of matrix metalloproteinases and cytokines are potential markers for oral carcinoma, infectious disease in the oral cavity, and systemic disease. Further research is required to monitor and predict potential salivary biomarkers for health and disease in clinical practice and precision medicine.

CRHR1 mediates the transcriptional expression of pituitary hormones and their receptors under hypoxia.

Hypothalamus-pituitary-adrenal (HPA) axis plays critical roles in stress responses under challenging conditions such as hypoxia, via regulating gene expression and integrating activities of hypothalamus-pituitary-targets cells. However, the transcriptional regulatory mechanisms and signaling pathways of hypoxic stress in the pituitary remain to be defined. Here, we report that hypoxia induced dynamic changes in the transcription factors, hormones, and their receptors in the adult rat pituitary. Hypoxia-inducible factors (HIFs), oxidative phosphorylation, and cAMP signaling pathways were all differentially enriched in genes induced by hypoxic stress. In the pituitary gene network, hypoxia activated c-Fos and HIFs with specific pituitary transcription factors (Prop1), targeting the promoters of hormones and their receptors. HIF and its related signaling pathways can be a promising biomarker during acute or constant hypoxia. Hypoxia stimulated the transcription of marker genes for microglia, chemokines, and cytokine receptors of the inflammatory response. Corticotropin-releasing hormone receptor 1 (CRHR1) mediated the transcription of Pomc, Sstr2, and Hif2a, and regulated the function of HPA axis. Together with HIF, c-Fos initiated and modulated dynamic changes in the transcription of hormones and their receptors. The receptors were also implicated in the regulation of functions of target cells in the pituitary network under hypoxic stress. CRHR1 played an integrative role in the hypothalamus-pituitary-target axes. This study provides new evidence for CRHR1 involved changes of hormones, receptors, signaling molecules and pathways in the pituitary induced by hypoxia.