Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary.

We studied the distribution of messenger RNA (mRNA) that encodes for vascular endothelial growth factor (VEGF) within the primate ovary by in situ hybridization and Northern analysis to determine if the presence of mRNA for this angiogenic factor is associated with structures within the ovary in which angiogenesis is thought to play a role in development and/or function. In situ hybridization to sections of cynomolgus ovaries with a 35S-labeled antisense RNA probe revealed specific tissue localization within the follicle as well as the corpus luteum, but not stromal tissue. Intense expression of mRNA for VEGF during the late follicular phase was confined to the maturing follicle which, we presume, was destined for ovulation. Hybridization within the corpus luteum exhibited a punctate pattern suggesting that there may be specific cells within the corpus luteum that express mRNA for VEGF. The expression of mRNA for VEGF during the early and late luteal phase of the menstrual cycle was studied by Northern analysis. Messenger RNAs were detectable at approximately 3.7 and 5.0 kb positions in corpora lutea collected during the early luteal phase of the menstrual cycle (days 3-5 postovulation). No hybridization signals were observed with RNA prepared from regressing corpora lutea (1-2 days following the onset of menses). The gonadotropic regulation of the expression of mRNA for VEGF in the corpus luteum was studied by treating monkeys with a potent GnRH antagonist during the midluteal phase of the menstrual cycle. Administration of the antagonist for 1 or 2 days did not alter the expression of mRNA for VEGF in comparison to corresponding controls. However, a 3-day treatment regimen brought about a significant reduction in the levels of mRNA for VEGF (P less than 0.01). These studies demonstrate a development-related expression of mRNA for VEGF in the ovary during the menstrual cycle and are consistent with the hypothesis that VEGF may play important roles in follicle selection and corpus luteum function in primates.

[1]  J. Richards,et al.  Hormonal regulation of luteinizing hormone/chorionic gonadotropin receptor mRNA in rat ovarian cells during follicular development and luteinization. , 1990, Molecular endocrinology.

[2]  D. Connolly,et al.  Vascular permeability factor, an endothelial cell mitogen related to PDGF. , 1989, Science.

[3]  D. Gospodarowicz,et al.  Production a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Koos,et al.  Factors That May Regulate the Growth and Regression of Blood Vessels in the Ovary , 1983 .

[5]  A. L. Goodman,et al.  Preliminary characterization of angiogenic activity in media conditioned by cells from luteinized rat ovaries. , 1990, Endocrinology.

[6]  A. Mason,et al.  Localization of inhibin/activin subunit mRNAs within the primate ovary. , 1990, Molecular endocrinology.

[7]  D. Gospodarowicz,et al.  Structural characterization and biological functions of fibroblast growth factor. , 1987, Endocrine reviews.

[8]  A. Zeleznik,et al.  The corpus luteum of the primate menstrual cycle is capable of recovering from a transient withdrawal of pituitary gonadotropin support. , 1985, Endocrinology.

[9]  J. Fiddes,et al.  Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. , 1986, Science.

[10]  A. L. Goodman,et al.  Evidence for a Non-Steroidal Angiotropic Factor from the Primate Corpus Luteum: Stimulation of Endothelial Cell Migration in Vitro , 1985, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[11]  E. Simpson,et al.  Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. , 1990, The Journal of clinical endocrinology and metabolism.

[12]  D. Goeddel,et al.  Vascular endothelial growth factor is a secreted angiogenic mitogen. , 1989, Science.

[13]  R. Mitchell,et al.  Bovine granulosa cells produce basic fibroblast growth factor. , 1987, Endocrinology.

[14]  The Role of Lipoproteins in the Regulation of Progesterone Secretion by the Human Corpus Luteum , 1982, Fertility and sterility.

[15]  J. Winer,et al.  The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. , 1991, Molecular endocrinology.

[16]  P. Oehme,et al.  Demonstration of angiogenesis-activity in the corpus luteum of cattle. , 1977, Experimentelle Pathologie.

[17]  H. Fraser,et al.  Suppression of luteal function by a luteinizing hormone-releasing hormone antagonist during the early luteal phase in the stumptailed macaque monkey and the effects of subsequent administration of human chorionic gonadotropin. , 1987, Endocrinology.

[18]  A. Zeleznik,et al.  Gonadotropin-binding sites in the rhesus monkey ovary: role of the vasculature in the selective distribution of human chorionic gonadotropin to the preovulatory follicle. , 1981, Endocrinology.

[19]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[20]  G. Niswender,et al.  Blood flow: a mediator of ovarian function. , 1976, Biology of reproduction.

[21]  J. Richards,et al.  Cholesterol side-chain cleavage P450 messenger ribonucleic acid: evidence for hormonal regulation in rat ovarian follicles and constitutive expression in corpora lutea. , 1987, Endocrinology.

[22]  A. Zeleznik,et al.  Ovarian responses in macaques to pulsatile infusion of follicle-stimulating hormone (FSH) and luteinizing hormone: increased sensitivity of the maturing follicle to FSH. , 1986, Endocrinology.

[23]  G. Corner The histological dating of the human corpus luteum of menstruation. , 1956, The American journal of anatomy.

[24]  H. Phillips,et al.  Vascular endothelial growth factor is expressed in rat corpus luteum. , 1990, Endocrinology.

[25]  D. Connolly,et al.  Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. , 1989, The Journal of clinical investigation.