AJP - Endocrinology and Metabolism, Vol 257, Issue 3 E318-E322, Copyright © 1989 by American Physiological Society
Cyclic nucleotides and polyamines in prolactin stimulation of lactose biosynthesis
C. A. Oppat and J. A. Rillema
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
The possible roles of adenosine 3',5'-cyclic monophosphate (cAMP) and
guanosine 3',5'-cyclic monophosphate (cGMP) and of polyamines on the early
effect of prolactin (PRL) on lactose biosynthesis have been investigated in
cultured mammary gland explants derived from mice 12-14 days pregnant.
Elevated cAMP concentrations impaired the PRL stimulation of [3H]glucose
incorporation into lactose. Adding dibutyryl cAMP (0.1-0.5 mM) or
phosphodiesterase inhibitors [methyl isobutylxanthine (0.1-0.5 mM) or
theophylline (0.5-5.0 mM)] to the culture medium abolished the PRL
response. The addition of 8-bromo cGMP (0.5 mM) with or without 1.0 mM
spermidine had no effect on the PRL stimulation of lactose synthesis. By
itself, 1.0 mM spermidine consistently produces a small but significant
PRL-like stimulation of lactose synthesis in this system. Ongoing polyamine
metabolism appears to be necessary for the PRL effect on lactose synthesis
because 100 microM methylglyoxal bis(guanyl hydrazone), an inhibitor of
S-adenosyl methionine decarboxylase, abolished the PRL response.
alpha-Difluoromethylornithine, an inhibitor of ornithine decarboxylase
activity, at concentrations from 1.0 to 10 mM had no effect on the PRL
stimulation of lactose synthesis.
