Okuma Y, O'Connor A E, Muir J A, Stanton P G, de Kretser D M, Hedger M P
Monash Institute of Medical Research, Monash University, Melbourne, Australia.
J Endocrinol. 2005 Oct;187(1):125-34. doi: 10.1677/joe.1.06266.
The regulation of Sertoli cell activin A and inhibin B secretion during inflammation was investigated in vitro. Adult rat Sertoli cells were incubated with the inflammatory mediators, lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), IL-6 and the IL-1 receptor antagonist (IL-1ra) over 48 h in culture. Activin A, inhibin B and IL-1alpha were measured in the culture medium by specific two-site ELISAs. Both IL-1beta- and LPS-stimulated activin A and inhibited inhibin B secretion. LPS also stimulated the production of IL-1alpha in the cultures. In contrast to IL-1beta, IL-6 had no effect on activin A, although it did have a significant inhibitory effect on inhibin B secretion. Ovine follicle-stimulating hormone (FSH) and the cAMP analogue dibutyryl cAMP opposed the actions of IL-1 and LPS by suppressing activin A and IL-1alpha secretion and by stimulating inhibin B. Blocking IL-1 activity in the cultures by addition of an excess of IL-1ra completely prevented the response of activin A to exogenous IL-1beta, and reduced the response to LPS by 50%. In the presence of IL-1ra, basal secretion of inhibin B was increased, but IL-1ra was unable to reverse the suppression of inhibin B by LPS. These data indicate the importance of both IL-1 isoforms in regulating secretion of activin A and inhibin B by mature Sertoli cells during inflammation. The data also establish that inflammation exerts its effects on activin A and inhibin B secretion via other pathways in addition to those mediated by IL-1, and that hormonal stimulation by FSH and cAMP moderates the Sertoli cell response to inflammation. Interference with the complex interactions between these cytokines and hormones may contribute to the disruption of reproductive function that can accompany infection and illness in men.
在体外研究了炎症期间支持细胞激活素A和抑制素B分泌的调节。成年大鼠支持细胞在培养中与炎症介质脂多糖（LPS）、白细胞介素-1β（IL-1β）、IL-6和IL-1受体拮抗剂（IL-1ra）一起孵育48小时。通过特异性双位点酶联免疫吸附测定法测量培养基中的激活素A、抑制素B和IL-1α。IL-1β和LPS均刺激激活素A分泌并抑制抑制素B分泌。LPS还刺激培养物中IL-1α的产生。与IL-1β不同，IL-6对激活素A无影响，尽管它对抑制素B分泌有显著抑制作用。绵羊促卵泡激素（FSH）和环磷酸腺苷（cAMP）类似物二丁酰cAMP通过抑制激活素A和IL-1α分泌以及刺激抑制素B来对抗IL-1和LPS的作用。通过添加过量的IL-1ra阻断培养物中的IL-1活性可完全阻止激活素A对外源性IL-1β的反应，并使对LPS的反应降低50%。在存在IL-1ra的情况下，抑制素B的基础分泌增加，但IL-1ra无法逆转LPS对抑制素B的抑制作用。这些数据表明两种IL-1亚型在炎症期间调节成熟支持细胞激活素A和抑制素B分泌中的重要性。数据还表明，炎症除了通过IL-1介导的途径外，还通过其他途径对激活素A和抑制素B分泌产生影响，并且FSH和cAMP的激素刺激可调节支持细胞对炎症的反应。干扰这些细胞因子和激素之间的复杂相互作用可能导致男性感染和疾病时伴随的生殖功能紊乱。
