Estrogen Production by Luteal Cells Isolated from Rhesus Monkeys during the Menstrual Cycle: Correlation with Spontaneous Luteolysis*

Abstract

To assess the hypothesis that luteolysis in primates may occur as a consequence of estrogen secretion by the corpus luteum, the production of estradiol (E₂), estrone (E₁), and progesterone (P) was examined in suspensions of luteal cells isolated from corpora lutea of rhesus monkeys at various stages of the menstrual cycle. Cells were obtained on days 16–19 (5-7 days after the preovulatory LH peak), days 21-22 (8-10 days after the LH surge), and days 23-25 (11-14 days after the LH surge) of the menstrual cycle. Under basal conditions (no exogenous hormones), day 16–19 cells secreted picogram quantities (per 5 × 10⁴ cells/ml nutrient medium) of E₂ and E₁ compared to nanogram amounts of P for up to 6 h in vitro. Estrogen production by day 16–19 cells was significantly (P < 0.05) enhanced by as little as 0.1 ng/ml hCG, with a maximal response at 100 ng/ml. Under basal conditions, day 16–19 cells produced significantly greater amounts of E₂ than E₁, whereas day 21-22 cells synthesized similar quantitites of these estrogens due to a reduction in E₂ production. Basal P and E₁ productions by day 16–19 and day 21-22 cells were similar. In the presence of hCG, E₂ and P production by day 21-22 cells was significantly (P < 0.05) less than that by day 16–19 cells. However, hCG-stimulated E₁ production remained unchanged. Day 23-25 cells produced significantly (P < 0.01) less P, E₂, and E, than day 16-19 cells and failed to respond to hCG. Incubation with testosterone (T; 1-100 ng/ml) or androstenedione (A) but not dihydrotestosterone markedly increased estrogen synthesis by day 16-19 cells without altering P secretion. Day 16-19 cells and day 21-22 cells produced primarily E₂ during incubation with T. In contrast, A enhanced both E₂ and E₁ production by day 16-19 cells and primarily E₁ production by day 21-22 cells. Incubation with pregnenolone but not P enhanced luteal cell E₂ and E₁ production in a manner similar to incubation with A. The addition of hCG failed to enhance estrogen production in the presence of T or A. The data indicate that the estrogen synthetic capacity of luteal cells from the rhesus monkey did not increase around the time of luteolysis but decreased coincident with declining P secretion. However, luteal cell conversion of precursors to E₂ and E₁ suggests that changes in the level or form of estrogen in the corpus luteum in vivo could occur just before luteolysis due to modulation of the aromatizing enzyme system or the availability of androgen in luteal cells. (Endocrinology106: 519, 1980)