Angiogenesis and its Hormonal Control in the Corpus Luteum of the Pregnant Rat1

Beginning on Day 8 of pregnancy (Day 1 = sperm in vaginal smear), rats were injected i.p. with 3H thymi-dine (TDR), killed 3 h later, and corpora lutea (CL) were dissected and saved for determining radioactivity in the acid-insoluble fraction or for autoradiography to determine labeling index (LI) of luteal and endothelial cells. An approximate doubling in DNA content in CL occurred between Days 13 and 14, with a high level maintained through Day 23. This was reflected in an abrupt increase in 3H TDR incorporation on Day 13, with the peak reached on Day 14 and a subsequent decline to baseline values on Day 18. Autoradiography revealed that the LI of luteal endothelial cells rose from 2.1% on Day 12 to 10.0% on Day 14, and the LI of luteal cells correspondingly increased from 0.3% to 2.3%. Hypophysectomy (H̄) on Day 12 resulted, by Day 14, in no change in serum progesterone (P4) and TDR incorporation and LI of endothelial cells. However, after H̄ and hysterectomy (HS̄) on Day 12, by Day 14, animals had low values for LI of endothelial and luteal cells, 3H TDR incorporation and serum P4. After H̄ + HS̄ at Day 12, animals injected daily with estradiol cyclo-pentylpropionate (200 µg/day) on Days 12–14 had serum P4, 3HTDR incorporation and LI of endothelial cells comparable to intact controls but not to luteal cells. However, similar treatment with testosterone cypionate (200 µg/day) or P4 (10 mg/day) did not maintain 3H TDR incorporation or LI of either cell type, although serum P4 and estradiol levels were restored to normal values. Prolactin (200 µg/day) did not affect any of these parameters. Human chorionic gonadotropin (hCG) (2 IU/day) restored serum P4 and LI of endothelial cells but not 3H TDR incorporation or LI of luteal cells. These results indicate that although in mid-pregnancy the increase in serum P4 is paralleled by endothelial hyperplasia, these phenomena are controlled by different mechanisms. Luteal proliferation of endothelial cells is induced by placental luteinizing hormone (LH)-like hormones and the effect is mediated by estrogen. Whether estrogens act directly on the endothelial cells or via intermediate growth factors is unknown.