Functional evidence for divergent receptor activation mechanisms of luteotrophic and luteolytic events in the human corpus luteum.
Using a dispersed human luteal cell culture model, progesterone synthesis following treatment by incremental doses of human chorionic gonadotrophin (HCG) and the stable prostaglandin F2alpha (PGF2alpha) analogue cloprostenol, alone or in combination, was related to corpora lutea (CL) mRNA transcript abundance coding for the luteinizing hormone (LH)/HCG receptor (LH-R) and PGF2alpha-receptor (FP) by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in 33 otherwise healthy women, scheduled for surgery due to benign conditions. CL were grouped according to age, based on the occurrence of a preovulatory LH surge where post-LH days 2-5 were designated as early luteal phase, days 6-10 as mid-luteal phase and days 11-14 as late luteal phase. When exposed to HCG, maximal progesterone output was raised 2.2-fold (P = 0.08, n = 5) compared with untreated controls in the early CL, while it increased 5.7- and 4.6-fold in the mid- and late groups respectively (P<0.05, n = 4 mid-luteal phase, n = 3 late luteal phase). This stimulation pattern was found to be concordant with the value of mRNA coding for LH-R in all groups (n = 6 early luteal phase, n = 5 mid-luteal phase, n = 6 late luteal phase). The integrated response to HCG and cloprostenol showed a dose-dependent 60% inhibition of progesterone production; but only in late luteal phase luteal cells (P<0.01, n = 3). FP mRNA values were lowest in early luteal phase, and increased with the age of the CL. Interestingly, lowest CL tissue concentrations of the natural FP agonist PGF2alpha were found during mid-luteal phase while it increased again 1.6-fold during late luteal phase (P<0.05, n = 8 versus mid-luteal phase, n = 6). Collectively, these data demonstrate that (i) the extrinsic functional control (or rescue of CL in the event of pregnancy) occurs when the sensitivity towards LH/HCG is maximal; and (ii) the demise of CL function is mediated via an acquisition of sensitivity towards the intrinsic luteolytic signal, PGF2alpha in the ageing CL.
Ottander
U
U
Department of Obstetrics and Gynecology, Umeå University Hospital, Sweden.
Leung
C H
CH
Olofsson
J I
JI
D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology; D003008:Cloprostenol / Q000494:pharmacology; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D011374:Progesterone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D011974:Receptors, LH; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D003008:Cloprostenol; D011374:Progesterone; D015237:Dinoprost