The regulation of murine mammary tumor virus (MuMTV) production by mammotropic
hormones, hormonomimetic substances, and
cyclic nucleotides was investigated. The virus produced in control and treated mammary
tumor cell cultures was quantitated by measuring the supernatant
reverse transcriptase activity in exogenous reaction using
poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic
glucocorticoid,
dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of
cyclic AMP had no effect on spontaneous MuMTV production, whereas the
drug potentiated suboptimal concentrations of the
glucocorticoid. Natural
prostaglandins, potent agonists of
adenylate cyclase catalyzing intracellular synthesis of
cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of
prostaglandins decreased in the order of
PGA1 greater than
PGE1 greater than
PGB1 greater than
PGF2 alpha.
Prostaglandins can be replaced partially by
norepinephrine and
isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production.
Theophylline, an antagonist of
cAMP-phosphodiesterase converting cAMP to
AMP, enhanced the virus-stimulating activity of DXMT as well as of
prostaglandins. The enhancement of MuMTV production by
adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with
PGE1 and
norepinephrine. The results indicate that besides
hormones, other
hormone-like substances and
cyclic nucleotides may be involved in the complex mechanism of
hormone-regulated MuMTV genome expression.