Lymphokines, including interleukin-2, alter gonadotropin-stimulated progesterone production and proliferation of human granulosa-luteal cells in vitro.
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 (HPL-CM). 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 less than 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 down-stream 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.
Wang
L J
LJ
Department of Obstetrics and Gynaecology, Queen Elizabeth Hospital and Medical School, University of Adelaide, Woodville, South Australia.
Robertson
S
S
Seamark
R F
RF
Norman
R J
RJ
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003338:Corpus Luteum / Q000166:cytology / Q000378:metabolism*; D003470:Culture Media; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D003470:Culture Media; D007375:Interleukin-1; D007376:Interleukin-2; D008222:Lymphokines; D005576:Colforsin; D011374:Progesterone