Related Experiment Videos
Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal
1Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Abstract:
The aim of this study was to investigate whether mouse placenta produces mature mouse GHRF (mGHRF) and whether cytokines regulate placental mGHRF production. Using Sephadex G-50 gel filtration chromatography and reverse phase HPLC, we identified immunoreactive mGHRF in acid-ethanol extract of placental tissues, which had chromatographic characteristics identical to those of hypothalamic mature mGHRF peptide. The major peak of immunoreactive GHRF in the medium from cultured placental cells was resolved by HPLC at a fraction identical to hypothalamic mature mGHRF. Interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin-M, which all use gp130 as a signal transducer, significantly inhibited mGHRF secretion by cultured placental cells. However, IL-1 alpha and tumor necrosis factor-alpha had no effect on mGHRF secretion. Antibodies to IL-6 or IL-6 receptor completely blocked the inhibitory effect of IL-6 on mGHRF secretion. Anti-LIF, and oncostatin-M inhibited the expression of mGHRF messenger RNA. These results suggest that mouse placenta produces and releases the mature mGHRF, which is indistinguishable by chromatographic criteria from that produced by the hypothalamus, and that signals through gp130 lead to the inhibition of mGHRF production and release in the mouse placenta.
Insights
Mouse placenta produces mature growth hormone-releasing factor (mGHRF) identical to hypothalamic mGHRF. Cytokines signaling through gp130 inhibit placental mGHRF production and release.
Area of Science:
- Reproductive biology
- Endocrinology
- Molecular biology
Background:
- The production and regulation of growth hormone-releasing factor (GHRF) in the placenta are not fully understood.
- Investigating placental GHRF is crucial for understanding fetal growth and development.
Purpose of the Study:
- To determine if the mouse placenta produces mature mouse GHRF (mGHRF).
- To investigate the role of cytokines in regulating placental mGHRF production.
Main Methods:
- Sephadex G-50 gel filtration chromatography and reverse-phase HPLC were used to analyze placental extracts and cultured placental cell medium.
- Immunoreactivity was assessed to identify mGHRF.
- The effects of various cytokines (IL-6, IL-11, LIF, Oncostatin-M, IL-1α, TNF-α) on mGHRF secretion and mRNA expression were examined.
Main Results:
- Mature mGHRF, chromatographically identical to hypothalamic mGHRF, was identified in mouse placental tissues and released by cultured placental cells.
- Cytokines utilizing the gp130 signal transducer (IL-6, IL-11, LIF, Oncostatin-M) significantly inhibited mGHRF secretion.
- IL-6 inhibition was blocked by antibodies to IL-6 or its receptor, while LIF and Oncostatin-M reduced mGHRF mRNA expression.
Conclusions:
- The mouse placenta produces and releases mature mGHRF, indistinguishable from hypothalamic mGHRF.
- Cytokine signaling via gp130 plays a significant role in inhibiting placental mGHRF production and release.