Transitions in sarcomeric alpha-actin and cardiac myosin heavy chain (MHC) gene expression have been useful as molecular markers for the development of cardiac hypertrophy and failure. In simpler model systems, alpha-actin expression has been useful in delineating some of the molecular pathways responsible for its induction following growth stimulation in vitro. In this study, we report that the effects of adrenergic agonists on alpha-actin expression in neonatal cardiocytes is dependent upon the culture conditions. In cardiocytes plated at 5 x 10(4) cells/cm2, skeletal alpha-actin mRNA levels represent 47%, 37% or 42% of total sarcomeric alpha-actin accumulations following administrations of 4 microM norepinephrine (NE), isoproterenol (Iso), or phenylephrine (PE), respectively. Cultured cardiocytes treated with vehicle (ascorbate) only accumulated 19% skeletal alpha-actin. Under these tissue culture conditions, in contrast to data reported previously, skeletal alpha-actin expression is regulated by both alpha- and beta-adrenergic agonist stimulation. Furthermore, we present data showing that an endogenous anti-beta-MHC transcript is regulated by both pressure-overload- or thyroxine-induced cardiac hypertrophy. Although anti-beta-MHC transcripts do not play a major role in regulating beta-MHC gene expression, the presence of this antisense transcript is associated with a novel set of beta-MHC degradation products. In vitro studies, where oligonucleotides complementary to beta-MHC have been introduced into cardiomyocytes, show that the mRNA levels of beta-MHC are decreased by 14-21% within 72 h after addition of the oligonucleotides. This result together with the presence of beta-MHC degradation products suggest that endogenous anti-beta-MHC transcripts may be involved in a post-transcriptional regulatory mechanism affecting the steady-state levels of beta-MHC expression.