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Lymphokines, Including Interleukin-2, Alter Gonadotropin-Stimulated Progesterone Production and Proliferation of Human Granulosa-Luteal Cells in Vitro^*

Reproductive Medicine Unit, Department of Obstetrics and Gynaecology, Queen Elizabeth Hospital and Medical School, University of Adelaide Woodville, South Australia 5011

Address requests for reprints to: Dr. R. J. Norman, Department of Obstetrics and Gynecology, Queen Elizabeth Hospital, Woodville Road, Woodville, South Australia 5011.

The effects of human interleukin-1 (IL-1) and IL-2 on human granulosa-luteal cell progesterone production were examined with or without hCG stimulation in vitro. Human granulosa-luteal cells were recovered from follicular fluid obtained from women undergoing in vitro fertilization procedures and cultured for up to 7 days before supernatant progesterone level measurement.

Lymphokine-rich conditioned medium was prepared from mitogen-stimulated human peripheral blood leukocytes (HPLCM). The influence of HPL-CM on both granulosa-luteal cell progesterone production and cell growth was inhibitory. In contrast, supernatants of the IL-2-producing cell line MLA-144 (MLA-CM) stimulated both basal progesterone secretion and cell proliferation. Human recombinant IL-2 (from 0.1–100 IU) alone did not change progesterone levels, compared to control values, after 24 h of cell culture. However, 1, 10, and 100 IU IL-2 significantly inhibited progesterone secretion from cells stimulated by 5 IU hCG (P < 0.01). The enhanced progesterone levels stimulated by forskolin were also significantly inhibited by 10 IU IL-2 (P = 0.01). This effect was not mediated through decreased cAMP, since the forskolin-enhanced cAMP level was not influenced by IL-2. IL-1, with or without hCG, did not show any effect on progesterone production during either 24 or 48 h of cell culture.

It is concluded that 1) human recombinant IL-2 significantly inhibits progesterone production stimulated by hCG in human granulosa-luteal cells; 2) IL-2 also had a marked inhibitory effect on forskolin-induced progesterone release, but did not influence the increased cAMP level stimulated by forskolin; 3) the inhibitory influence of IL-2 on progesterone synthesis may be downstream in the signal transduction pathway from cAMP activation; and 4) HPL-CM and MLA-CM produced inhibitory and stimulatory effects, respectively, on both basal and hCG-stimulated progesterone levels as well as on granulosa-luteal cell proliferation. These activities cannot be completely attributed to IL-2, and other mediators of leukocyte origin may, therefore, exist. (J Clin Endocrinol Metab 72: 824–831, 1991)

^* This work was supported by the University of Adelaide.

Received May 8, 1990.

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