AJP - Endocrinology and Metabolism, Vol 264, Issue 3 E471-E475, Copyright © 1993 by American Physiological Society
Parathyroid hormone-related protein increases cAMP production in mammary epithelial cells
S. Ferrari, R. Rizzoli, C. Chaponnier, G. Gabbiani and J. P. Bonjour
Department of Medicine, University Hospital, Geneva, Switzerland.
Parathyroid hormone-related protein (PTHrP) is a major cause of malignant
hypercalcemia but has been found in many nontumoral tissues as well. Thus
it is produced by the mammary gland during lactation and released into
milk. Whether PTHrP directly affects breast tissue is however not known. We
investigated the effects of PTHrP on adenosine 3',5'-cyclic monophosphate
(cAMP) production in primary cultures of mammary epithelial cells isolated
from lactating rats. On the 7th day in culture, synthetic PTHrP-(1-34),
recombinant (r) PTHrP-(1-108), and rPTHrP-(1-141) stimulated cAMP
production in a concentration-dependent manner. Thus PTHrP-(1-34) induced a
1.92 +/- 0.04-fold stimulation of cAMP production (mean +/- SE, n = 5
separate experiments, P < 0.001). At the time of maximal responsiveness
to PTHrP, a significant proportion of the cells was characterized by an
elongated shape and a positive immunofluorescent staining for both
prekeratin and alpha-smooth muscle actin 1, compatible with a myoepithelial
phenotype. It therefore appears that PTHrP can stimulate the production of
cAMP in mammary cells, suggesting a possible autocrine/paracrine regulatory
function for PTHrP in breast tissue.
