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Membrane signalling and progesterone in female and male osteoblasts. I. Involvement of intracellular Ca 2+ , inositol trisphosphate, and diacylglycerol, but not cAMP
Author(s) -
Grosse Brigitte,
Kachkache Moustapha,
Le Mellay Véronique,
Lieberherr Michèle
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(20001101)79:2<334::aid-jcb160>3.0.co;2-m
Subject(s) - endoplasmic reticulum , phospholipase c , medicine , endocrinology , diacylglycerol kinase , pertussis toxin , inositol trisphosphate , inositol , biology , receptor , protein kinase c , microbiology and biotechnology , signal transduction , g protein
Bone is a target tissue of progestins, but the mechanisms by which they act are still unclear. We examined the early (5–60 s) effects of progesterone and progesterone covalently bound to BSA (P‐CMO BSA), which does not enter the cell, on the cytosolic free Ca 2+ concentration ([Ca 2+ ]i) and the formation of inositol 1,4,5 trisphosphate (InsP3) and diacylglycerol (DAG) in confluent female and male rat osteoblasts. P‐CMO BSA like free progesterone increased [Ca 2+ ]i via Ca 2+ influx through L‐type Ca 2+ channels and Ca 2+ mobilization from the endoplasmic reticulum. Both progestins increased InsP 3 and DAG formation within 10 s, and the increase was blocked by phospholipase C inhibitors (neomycin and U‐73122). Progesterone and P‐CMO BSA mobilized calcium from the endoplasmic reticulum via the activation of a phospholipase C linked to a pertussis toxin‐insensitive G‐protein in both osteoblast types, and this process was controlled by protein kinase C. Neither progestin had any effect on cAMP formation in male and female osteoblasts. The membrane effects were not blocked by a progesterone nuclear antagonist. They were independent of the concentration of nuclear receptors and not linked to gender. Thus, progesterone appears to act in female and male rat osteoblasts via unconventional cell‐surface receptors which belong to the class of membrane receptors coupled to phospholipase C via a pertussis toxin‐insensitive G‐protein. The bifurcating pathways leading to the formation of InsP 3 and DAG may provide a certain flexibility in controlling cell responses, both by their nature and by their rates of formation and degradation. J. Cell. Biochem. 79:334–345, 2000. © 2000 Wiley‐Liss, Inc.