TY - JOUR
T1 - Influence of ovarian ornithine decarboxylase in folliculogenesis and luteinization
AU - Bastida, Carmen M
AU - Cremades, Asunción
AU - Castells, Maria T
AU - López-Contreras, Andrés J
AU - López-García, Carlos
AU - Tejada, Francisco
AU - Peñafiel, Rafael
PY - 2005/2/1
Y1 - 2005/2/1
N2 - LH plays a relevant role in folliculogenesis, ovulation, and luteinization. Although ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is a target of LH in the ovary, the functional significance of ODC induction has remained elusive. Our study reveals that the blockade of the induction of ovarian ODC by means of the specific inhibitor alpha-difluoromethylornithine (DFMO) affects folliculogenesis and luteinization. In immature female mice, DFMO was found to inhibit ovarian growth, the formation of Graafian follicles, and the secretion of progesterone and estradiol. In adult cycling females, the administration of DFMO on the evening/night of proestrus markedly decreased plasma progesterone levels at diestrus, which was associated to the decrease in the expression of steroidogenic factor 1, cytochrome cholesterol side chain cleavage enzyme, and steroidogenic acute regulatory protein in the ovary and to a reduced vascularization of the corpora lutea. These effects were not reverted by the administration of gonadotropins or prolactin. ODC immunoreactivity was also stimulated by LH in theca and granulosa cells of antral follicles but not in preantral follicles. Overall, these experiments demonstrate that elevated ODC values found in the ovary of immature and adult mice play a relevant function in ovarian physiology and that ODC/polyamines must be considered as important mediators of some of the effects of LH on follicular development and luteinization.
AB - LH plays a relevant role in folliculogenesis, ovulation, and luteinization. Although ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is a target of LH in the ovary, the functional significance of ODC induction has remained elusive. Our study reveals that the blockade of the induction of ovarian ODC by means of the specific inhibitor alpha-difluoromethylornithine (DFMO) affects folliculogenesis and luteinization. In immature female mice, DFMO was found to inhibit ovarian growth, the formation of Graafian follicles, and the secretion of progesterone and estradiol. In adult cycling females, the administration of DFMO on the evening/night of proestrus markedly decreased plasma progesterone levels at diestrus, which was associated to the decrease in the expression of steroidogenic factor 1, cytochrome cholesterol side chain cleavage enzyme, and steroidogenic acute regulatory protein in the ovary and to a reduced vascularization of the corpora lutea. These effects were not reverted by the administration of gonadotropins or prolactin. ODC immunoreactivity was also stimulated by LH in theca and granulosa cells of antral follicles but not in preantral follicles. Overall, these experiments demonstrate that elevated ODC values found in the ovary of immature and adult mice play a relevant function in ovarian physiology and that ODC/polyamines must be considered as important mediators of some of the effects of LH on follicular development and luteinization.
KW - 3-Hydroxysteroid Dehydrogenases/genetics
KW - Age Factors
KW - Animals
KW - Aromatase/genetics
KW - Cholesterol Side-Chain Cleavage Enzyme/genetics
KW - DNA-Binding Proteins/genetics
KW - Eflornithine/pharmacology
KW - Enzyme Inhibitors/pharmacology
KW - Estradiol/blood
KW - Female
KW - Follicle Stimulating Hormone/pharmacology
KW - Homeodomain Proteins
KW - Luteinization/metabolism
KW - Luteinizing Hormone/pharmacology
KW - Mice
KW - Mice, Inbred Strains
KW - Ornithine Decarboxylase/metabolism
KW - Ornithine Decarboxylase Inhibitors
KW - Ovarian Follicle/enzymology
KW - Phosphoproteins/genetics
KW - Progesterone/blood
KW - RNA, Messenger/analysis
KW - Receptors, Cytoplasmic and Nuclear
KW - Signal Transduction/physiology
KW - Steroidogenic Factor 1
KW - Transcription Factors/genetics
KW - Steroidogenic Acute Regulatory Protein
U2 - 10.1210/en.2004-1004
DO - 10.1210/en.2004-1004
M3 - Article
C2 - 15514084
SN - 0013-7227
VL - 146
SP - 666
EP - 674
JO - Endocrinology
JF - Endocrinology
IS - 2
ER -