Expression of leukemia inhibitory factor (LIF) and LIF receptor (LIF-R) inthe human adrenal cortex: implications for steroidogenesis

It is well established that steroidogenesis in the adrenal cortex is regula ted by extraadrenal factors, such as ACTH and angiotensin II. However, over the last years, it has become increasingly clear that paracrine and autocr ine mechanisms are also important for steroid synthesis in the adrenal glan d. The current study was designed to analyze whether the pleiotropic cytoki ne leukemia inhibitory factor (LIF) and/or its receptor (LIF-R) are express ed in the normal human adrenal cortex. and whether they may play a role in regulating steroidogenesis. Using LIF- and LIF-R-specific primers, we show by RT-PCR that both mRNAs are expressed in this tissue, as well as in the N CI-H295 adrenal carcinoma cell line. The correct sequences of the PCR produ cts were verified by restriction enzyme analysis and DNA sequencing. Immuno histochemistry, employing specific antibodies against LIF and LIF-R, reveal s expression of both proteins in the normal human adrenal cortex. Finally, we show that LIF can significantly enhance basal and ACTH-induced productio n of cortisol and aldosterone in NCI-H295 cells. In summary, we show for th e first time that LIF and its receptor are expressed in the normal human ad renal cortex. Our stimulation experiments indicate that the intraadrenal LI F/LIF-R system may participate in regulating adrenal steroidogenesis. (C) 2 000 Elsevier Science Ireland Ltd. All rights reserved.