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

In the classical theory of steroid hormone action, steroids diffuse through the membrane and alter transcription of specific genes resulting in synthe sis of proteins important for modulating cell function. Most often, steroid s 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 i n vitro. This action is accompanied by similarly rapid reductions in cellul ar Ca2+ and cAMP levels, second messengers known to transduce the membrane effects of peptide hormones. We further examined whether cortisol might inh ibit 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 mug/ml) was ineffective in overcoming PRL release induced by hyposm otic medium or that inhibited by cortisol over 4 h static incubations. Thes e 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. The se studies suggest that cortisol inhibits PRL release through a plasma memb rane-associated, protein-synthesis independent (non-genomic) pathway. (C) 2 001 Elsevier Science Inc. All rights reserved.