Roles of cyclic AMP and inositol phosphates in the luteolytic action of cloprostenol, a prostaglandin F2 alpha analogue, in marmoset monkeys (Callithrix jacchus).
The luteolytic response to a prostaglandin F2 alpha analogue, cloprostenol, was investigated in vivo and in vitro at defined stages of the luteal phase. In vivo administration of cloprostenol to female marmoset monkeys on day 3 after ovulation had no effect on plasma progesterone concentrations, whereas administration on day 14 after ovulation reduced plasma progesterone to preovulatory concentrations within 4 h. To identify the cellular basis for this luteolytic action, marmoset luteal tissue obtained on days 3, 6 and 14 after ovulation was incubated in vitro and progesterone production, cAMP accumulation and phosphoinositide (PI) turnover measured in response to cloprostenol, human chorionic gonadotrophin (hCG) with or without cloprostenol, or dibutyryl-cAMP with or without cloprostenol. Progesterone production was stimulated by both hCG and dbcAMP at all stages of the luteal phase. Although neither hCG nor dbcAMP had any significant effects on PI turnover, hCG also increased cAMP accumulation. In marmoset luteal tissue obtained on day 3 after ovulation, cloprostenol had no significant effect on basal or hCG/dbcAMP-stimulated progesterone production but significantly stimulated PI turnover. In contrast, on days 6 and 14 after ovulation, cloprostenol significantly inhibited hCG- and dbcAMP-stimulated progesterone production and the cAMP response to hCG, but had no significant effect on PI turnover. Since progesterone production by the marmoset corpus luteum depends on the luteotrophic support of luteinizing hormone (LH), these observations suggest that the luteolytic action of cloprostenol in vivo involves the inhibition of LH/hCG action at sites both prior and subsequent to cAMP accumulation. However, such luteolytic effects do not appear to require the generation of inositol phosphates by increased PI turnover.
Michael
A E
AE
MRC/AFRC Comparative Physiology Research Group, Institute of Zoology, London, UK.
Webley
G E
GE
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002144:Callithrix; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003008:Cloprostenol / Q000494:pharmacology*; D003338:Corpus Luteum / Q000187:drug effects*; D046508:Culture Techniques; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism / Q000502:physiology*; D008183:Luteal Phase / Q000502:physiology; D003341:Luteolysis / Q000187:drug effects*; D011374:Progesterone / Q000097:blood
D006063:Chorionic Gonadotropin; D007295:Inositol Phosphates; D003008:Cloprostenol; D011374:Progesterone; D003994:Bucladesine; D000242:Cyclic AMP