REGULATION OF ACTH-INDUCED STEROIDOGENESIS IN HUMAN FETAL ADRENALS BY RTNF-ALPHA

The presence of tumor necrosis factor type alpha (TNF-α) in different fetal tissue and adult adrenal extracts was investigated by radioimmunoassay (RIA). Measurable levels of TNF-α were found in 12/22 fetal adrenals, but in none of the seven adult adrenals studied. Since it is known that (i) steroidogenesis in fetal adrenals differs greatly from that in adult glands by having higher androgen/corticosteroid ratio, (ii) and that macrophage-derived factors may cause adrenocortical suppression, the effect of TNF-α on corticotropin-induced steroidogenesis in primary cultures of human fetal adrenals was studied. Results show that TNF-α effectively suppresses, the production of cortisol and shifts the steroid synthesis towards androgen production. The effect was not accompanied by any change in cell viability and could be neutralized by addition of polyclonal rabbit anti-TNF-α antiserum to cell cultures. These results suggest that TNF-α may take part in the regulation of human fetal steroidogenesis within the network of the fetoplacental unit via inhibition of the cortisol synthesis. © 1990.