|
| Mediator | Clinical context | Biological effects in relation to endocrine function |
|
| ↑ IL-1β | Benign and malignant thyroid disease, NTI [94, 95] | (i) Stimulation of IL-6 expression [49, 94, 95] |
| (ii) Induction of NTI in the rat [96] |
| (iii) No change in thyroid hormone level in human after blockade of IL-1R [97] |
| Adrenal response to stress [79] | (i) Increased release of NPY, NE, and EP from human chromaffin cells via MAPK-dependent mechanism and nitric oxide synthase activation [79] |
| Gonadal function | (i) Reduction in LH secretion from the anterior pituitary [98] |
| (i) GnRH/LH output | (ii) Inhibition of gonadotropin-stimulated granulosa and Leydig cell steroidogenesis [99, 100] |
| (ii) Steroidogenesis | |
|
| ↑ IL-6 (sIL-6R) | Response of the HPA axis to stress | (i) Stress-induced activation of ERK 1/2 and STAT3 pathways in adrenal chromaffin cells [85] |
| (ii) Stimulation of the adrenal cortex during somatic [101, 102] and mental stress [104, 105] |
| (iii) Stress-induced activation of the HPA axis via STAT3 [106, 107] |
| Pituitary senescence and tumor growth | (i) Increased VEGF production, tumor cell proliferation, and ECM remodeling [108–110] |
| (ii) Regulation of normal pituitary cell senescence [35] |
| PHPT [64, 65] | (i) Bone remodeling and growth plate closure via STAT and SHP2/MAPK pathways [30, 56] |
Thyroid disease:
Thyroiditis [94, 103], NTI [66–68], and thyroid carcinoma [94] | (i) Amiodarone-induced production of IL-6 by thyrocytes [70] |
| (ii) Inhibition of thyroid function in the presence of sIL-6R in cultured human thyroid follicles [111] |
| (iii) Suppression of D1- and D2-mediated T4-to-T3 conversion and increase in D3-mediated T3 (and T4) inactivation in human cells [69] |
| Gonadal function | (i) Suppression of GnRH and/or LH secretion [77] |
| (i) GnRH/LH output | (ii) Inhibition of gonadal steroidogenesis [112]; impaired expression of LHR mRNA during maturation of granulosa cells [113] |
| (ii) Steroidogenesis | (iii) Inhibition of meiotic DNA synthesis of spermatocytes [114] |
| (iii) Spermatogenesis | (iv) Altered Sertoli cell tight junction dynamics via MAPK and ERK cascade [115, 116] |
| (iv) BTB permeability | |
|
| ↑ TNF-α | Adrenal medulla response to stress | (i) Increased expression of IL-6 mRNA in cultured bovine chromaffin cells [80, 85] |
| Gonadal steroidogenesis | (i) Decreased StAR expression and T synthesis in Leydig cell [117]; decreased aromatase activity in granulosa cells [99] |
|
| ↑ VEGF (VEGF165) | POEMS syndrome [19, 21, 118, 20] | (i) No correlation between VEGF and thyroid hormone levels or between VEGF and testicular function [14, 39] |
| Pituitary tumor growth | (i) IL-6 stimulated an increase in VEGF production [109] |
|
