Cytokine induction of heat shock protein in human granulosa-luteal cells

The infiltration of leukocytes is a characteristic feature ofluteolysis in humans. Leukocytes are known to generate physiologicalinducers of cell stress such as cytokines which have been implicatedas mediators of functional luteal regression. In cells exposedto stress, a response characterized by an increase in heat shockprotein (HSP) synthesis occurs. Recently, the induction of HSP-70in rat luteal cells has been shown to inhibit luteinizing hormone(LH) and cAMP-sensitive progesterone production, possibly byinterfering with the translocation of cholesterol to the mitochondrialcytochrome P450_SCC. We therefore investigated whether HSP-70is induced in human granulosa-luteal cells and its relationshipto steroidogenesis. [³⁵S]Methionine labelling showed an increasein a 70 kDa protein after heat treatment which was demonstratedto be HSP-70 by Western analysis using monoclonal antibodiesagainst the constitutive and inducible forms of HSP-70. Inductionof HSP-70 in human granulosa-luteal cells was also seen withinterferon (IFN) (10 ng/ml), tumour necrosis factor (TNF)-