Cytokines and steroidogenesis.

Cytokines interfere with steroidogenesis at the level of the adrenals, testes, and ovaries. Within the adrenal, macrophages, and lymphocytes, physiologically widely infiltrating the adrenal cortex, and adrenocortical, and chromaffin cells produce cytokines, as IL-1, IL-6, TNFalpha, leukemia inhibitory factor (LIF), and IL-18 which have a key role in the immune-adreno-cortical communication. In addition to cytokines interacting with adrenal function, cytokine independent mechanisms are responsible for a cell to cell-mediated immune regulation of the adrenal. The importance of this immune-endocrine cross-talk becomes evident in the case of autoimmune and inflammatory diseases being necessary for an adequate adrenal stress response. Secretory products of macrophages are involved in the regulation of steroidogenesis, Sertoli cell activity, and germ cell survival in the human testes. In rats, IL-1 is involved in the paracrine regulation of Leydig cell steroidogenesis. IL-6 has been suggested to exert adverse effects on the male reproductive function, inducing persistent testicular resistance to luteinizing hormone (LH) action and/or suppression of Leydig cell steroidogenesis. Cytokines such as IL-8 and MCP-1 (monocyte chemotactic protein-1) are involved in follicular development and atresia, ovulation, steroidogenesis, and corpus luteum function. In undifferentiated ovarian cells TNF and IL-1 inhibit steroidogenesis, whereas in differentiated ovaries these cytokines stimulate progesterone synthesis. Some ovarian cancer cells secrete TNF and IL-1 which stimulate growth of these cells. In conclusion, cytokines interact with steroidogenesis in a systemic and complex manner, influencing development, function, and hormone production of the adrenals, testes, and ovaries.