Cortisol suppresses prolactin release through a non-genomic mechanism involving interactions with the plasma membrane.

Abstract In the classical theory of steroid hormone action, steroids diffuse through the membrane and alter transcription of specific genes resulting in synthesis of proteins important for modulating cell function. Most often, steroids work solely through the genome to exert their physiological actions in a process that normally takes hours or days to occur. In tilapia ( Oreochromis mossambicus ), cortisol inhibits prolactin (PRL) release within 10–20 min in vitro. This action is accompanied by similarly rapid reductions in cellular Ca 2+ and cAMP levels, second messengers known to transduce the membrane effects of peptide hormones. We further examined whether cortisol might inhibit PRL release through a non-genomic, membrane-associated mechanism using the protein synthesis inhibitor, cycloheximide, and a membrane impermeant form of cortisol, cortisol-21 hemisuccinate BSA (HEF/BSA). Cycloheximide (2 and 10 μg/ml) was ineffective in overcoming PRL release induced by hyposmotic medium or that inhibited by cortisol over 4 h static incubations. These dosages reduced protein synthesis as measured by amino acid incorporation in pituitaries by 75 and 99%, respectively. During 4-h incubation, HEF/BSA and HEF significantly reduced PRL release in a dose-dependent fashion. These studies suggest that cortisol inhibits PRL release through a plasma membrane-associated, protein-synthesis independent (non-genomic) pathway.