Distinct regulation of gene expression by prostaglandin F(2alpha) (PGF(2alpha)) is associated with PGF(2alpha) resistance or susceptibility in human granulosa-luteal cells.
The effects of human chorionic gonadotrophin (HCG) and prostaglandin F(2alpha) (PGF(2alpha)) on regulation of human granulosa-luteal cell (GLC) function at different stages of differentiation (day 2 versus day 8 of culture) were studied. Expression of LH receptor mRNA and biosynthesis of progesterone were HCG dependent in human GLC at all stages (n = 6, P < 0.05). Steady-state concentrations of mRNA encoding for FP (a specific high-affinity plasma membrane receptor for PGF(2alpha)) were not dependent on, but were stimulated by, addition of HCG (10 IU/ml) or 8-bromo-cAMP (0.5 mmol/l) (n = 6, P < 0.05). Treatment with PGF(2alpha) (100 nmol/l) decreased FP mRNA concentration, but had no effect on LH receptor and cyclo oxygenase-2 (COX-2) expression on day 2 of cultured GLC (n = 8). As a result, the progesterone biosynthesis by GLC was not affected. On day 8, PGF(2alpha) induced FP and PGHS-2 expression and at the same time decreased LH receptor expression, resulting in inhibition of progesterone output by GLC. Our data demonstrated that early stage GLC (day 2 of culture) are resistant to PGF(2alpha)-induced inhibition of progesterone synthesis but underwent further differentiation and acquired luteolytic capacity after 8 days culture in vitro. We conclude that, via distinct gene regulation at different stages of differentiation, human GLC may become resistant or susceptible to PGF(2alpha)-induced luteolysis.
Tsai
S J
SJ
Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China. Seantsai@mail.ncku.edu.tw
Wu
M H
MH
Chuang
P C
PC
Chen
H M
HM
D002455:Cell Division; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D011374:Progesterone / Q000096:biosynthesis*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger; D011974:Receptors, LH / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics*
D006063:Chorionic Gonadotropin; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D011974:Receptors, LH; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D011374:Progesterone; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases