Activation of the phosphatidylinositol pathway in the primate corpus luteum by prostaglandin F2 alpha.
The current study was designed to investigate the ability of prostaglandin F2 alpha (PGF2 alpha) to activate a second messenger system (phosphatidylinositol pathway) in corpora lutea (CL) of rhesus monkeys. Activation of this pathway was assessed by monitoring the hydrolysis of phosphatidylinositol to inositol phosphates. Since inositol triphosphate mobilizes intracellular Ca2+, intracellular free calcium concentrations ([Ca2+]i) were also assessed in individual cells by fura-2 fluorescence photometry. These responses to PGF2 alpha were measured in luteal cells collected from nonpregnant rhesus monkeys. CL were collected during the early (days 4-5 after estimated LH surge; n = 4), mid (days 8-9; n = 4), and late (days 13-14; n = 5) luteal phase and 1 day after in vivo hCG treatment (15 IU/dose, morning and evening), which began during the midluteal phase (n = 5). PGF2 alpha significantly increased the accumulation of inositol phosphates in all groups (P less than 0.05), except the midluteal phase (P = 0.07). The luteal sensitivity to PGF2 alpha, judged by phosphatidylinositol hydrolysis, was low in the early to midluteal phase compared to that in the late luteal phase and after in vivo hCG treatment. PGF2 alpha also caused a rapid, yet transient, increase in [Ca2+]i in a large proportion of primate luteal cells. The proportion of luteal cells that responded to PGF2 alpha with an increase in [Ca2+]i was smaller (P less than 0.05) in CL collected during the early luteal phase than in the other groups. Luteal progesterone production was inhibited by PGF2 alpha in CL collected after in vivo hCG. CL treated in vivo with hCG also displayed in vitro the largest increases in phosphatidylinositol hydrolysis and [Ca2+]i in response to PGF2 alpha. Therefore, this study demonstrates that PGF2 alpha is a potent activator of the phosphatidylinositol pathway in the primate CL. This activation is augmented as the luteal phase progresses and is influenced by in vivo hCG treatment. This study also provides evidence that the inhibitory effects of PGF2 alpha on progesterone production are associated with the activation of the phosphatidylinositol pathway.
Houmard
B S
BS
Department of Dairy Science, Ohio State University, Columbus 43210.
Guan
Z
Z
Stokes
B T
BT
Ottobre
J S
JS
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism; D008183:Luteal Phase / Q000502:physiology; D008253:Macaca mulatta; D010716:Phosphatidylinositols / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis; D015290:Second Messenger Systems / Q000187:drug effects*
D006063:Chorionic Gonadotropin; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011374:Progesterone; D015237:Dinoprost; D016257:Fura-2