The present study examined the role of progesterone in regulating human granulosa cell proliferation. Human granulosa and luteal cells were obtained from follicular aspirates of women undergoing in vitro fertilization. Cells were plated at 5, 10, or 50 x 10(3) cells/mL and cultured for up to 6 days. At specific times, cells were harvested and assessed for cell number and morphology. The medium was assayed for progesterone. Cells plated at 50 x 10(3) cells/mL did not increase in number after 3 or 6 days of culture, but rapidly differentiated, secreting high amounts of progesterone (> or = 320 nmol/L). Conversely, cells plated at 5 x 10(3) or 10 x 10(3) cells/mL doubled in number over the first 3 days of culture and subsequently differentiated. The addition of 100 ng/mL progesterone or more to the medium inhibited proliferation. Aminoglutethamide blocked progesterone secretion and increased the number of cells present after 3 days of culture. The antiproliferative effects of progesterone were not mimicked by estradiol, testosterone, dihydrotestosterone, or dexamethasone and could not be overridden by epidermal growth factor, a potent mitogen. These data suggest that progesterone plays an autocrine/paracrine role in regulating granulosa cell proliferation.
To further elucidate the role of progesterone in regulating granulosa cell function, human granulosa and luteal cells were obtained from follicular aspirates of women undergoing in vitro fertilization and placed in culture. Cells plated at 5 x 10(3) cells/mL doubled after 3 days. In contrast, cells plated at 50 x 10(3) cells/mL did not proliferate, but differentiated, secreting high levels of progesterone. Cells plated at 5 x 10(3) cells/mL and cultured with spent medium from cells plated at 50 x 10(3) cells/mL did not increase in number over 3 days of culture. The growth-inhibiting action of the spent medium was removed by either RU 486 (a progesterone receptor antagonist) or charcoal extraction, but not by heat inactivation. The addition of progesterone to fresh medium also prevented cell proliferation. Progesterone's ability to inhibit cell division was attenuated by either RU 486 or aminoglutethamide, which blocked progesterone synthesis. Further, epidermal growth factor (EGF) stimulated cell proliferation, and continuous exposure to progesterone blocked EGF-induced mitosis. When progesterone was added 2 h after EGF, it did not block EGF-stimulated cell proliferation. Progesterone also increased the percentage of granulosa cells and decreased the percentage of large luteal cells present after 3 days of culture, indicating that progesterone inhibited differentiation. Progesterone's effect on differentiation was dose dependent, reversible, and could be overridden by hCG or 8-bromo-cAMP. These observations suggest that progesterone acts directly on granulosa cells through its receptor to inhibit mitosis and that progesterone mediates its antiproliferative effects within 2 h of mitotic stimulation. Progesterone also blocks differentiation, but this effect of can be overcome by hCG or cAMP analogs. These data indicate that progesterone plays a major role in controlling the number of luteal cells that ultimately develop within a corpus luteum by regulating both granulosa cell proliferation and differentiation.
With the increasing use of expectant or laparoscopic management of cystic adnexal masses in postmenopausal women, adequate preoperative evaluation and assessment of malignant potential assume a critical role. Ultrasonography has become a cornerstone in this evaluation process. We describe a case of ultrasonographically identified bilateral cystic adnexal masses that at laparoscopy appeared to be massively dilated pelvic varicosities. In a postmenopausal patient, especially if a prior history of venous stasis is elicited, pelvic varicosities should be considered in the differential diagnosis of ultrasonographically diagnosed cystic adnexal masses. (J GYNECOL SURG 9:49, 1993) Address reprint requests to:
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