TY - JOUR
T1 - Role of ornithine decarboxylase in granulosa-cell replication and steroidogenesis in vitro
AU - Veldhuis, Johannes D.
AU - Hammond, James M.
N1 - Funding Information:
DL-alpha-difluoromethyl-ornithine was provided generously by Centre de Recherche, Merrell International, Strasbourg (France). Cyanoketone was a gift from the Upjohn Co. (Thomas J. Lobl, Ph.D.), Kalamazoo, MI. We thank the Shamokin Packing Corp. for porcine ovaries, Marlene Thompson for the preparation of this manuscript, and Patricia Klase for radioimmunoassay of steroids. This work was supported by an NIH Grant (#HD10122) and a National Research Service Award (#lF332HD05755) (to J.D. Veldhuis) from NICHD.
PY - 1979/12/14
Y1 - 1979/12/14
N2 - We investigated the role of ornithine decarboxylase in ovarian steroidogenesis and granulosa-cell replication under basal and hormonestimulated conditions in vitro. Enzyme activity was markedly (>95 or >99%) reduced by DL-difluoromethyl-ornithine or 1,3-diaminopropane, which significantly impaired granulosa-cell replication in log-phase cultures. However, inhibition of ornithine decarboxylase activity augmented basal and hormonestimulated steroid production per cell, an effect abolished by cyanoketone, a specific inhibitor of steroid synthesis. Both the anti-proliferative and the steroidogenic effects of enzyme inhibition were substantially reversed by putrescine, the end-product of the reaction. Thus, ornithine decarboxylase, or polyamines, may be required for granulosa-cell replication, while deprivation of these compounds facilitates the expression of more differentiated cell function, such as steroid synthesis.
AB - We investigated the role of ornithine decarboxylase in ovarian steroidogenesis and granulosa-cell replication under basal and hormonestimulated conditions in vitro. Enzyme activity was markedly (>95 or >99%) reduced by DL-difluoromethyl-ornithine or 1,3-diaminopropane, which significantly impaired granulosa-cell replication in log-phase cultures. However, inhibition of ornithine decarboxylase activity augmented basal and hormonestimulated steroid production per cell, an effect abolished by cyanoketone, a specific inhibitor of steroid synthesis. Both the anti-proliferative and the steroidogenic effects of enzyme inhibition were substantially reversed by putrescine, the end-product of the reaction. Thus, ornithine decarboxylase, or polyamines, may be required for granulosa-cell replication, while deprivation of these compounds facilitates the expression of more differentiated cell function, such as steroid synthesis.
UR - http://www.scopus.com/inward/record.url?scp=0018642127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0018642127&partnerID=8YFLogxK
U2 - 10.1016/0006-291X(79)91946-6
DO - 10.1016/0006-291X(79)91946-6
M3 - Article
C2 - 526280
AN - SCOPUS:0018642127
SN - 0006-291X
VL - 91
SP - 770
EP - 777
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -