Antagonistic Interactions of Adenosine and Prostaglandin _2α Modulate Acute Responses of Luteal Cells to Luteinizing Hormone

In dispersed rat luteal cells in short term incubation (90 min), adenosine amplified cAMP accumulation and progesterone secretion in repsonse to LH in a dose-dependent manner. In the absence of LH, only a small effect of adenosine was seen. For LH-stimulated cAMP accumulation, amplifcation was seen with doses as low as 1 μM adenosine, and the ED₅₀ for adenosine was about 25 μM. Adenosine (50 μM) had little effect on ED₅₀ of LH (150 ng/ml) for stimulation of cAMP accumulation, but increased the maximal response to LH (1 μg/ml) by more than 10-fold. For LH-stimulated progesterone secretion, adenosine decreased the ED₅₀ for LH (30 ng/ml) by 2-fold and increased the maximum response to LH (100 ng/ml) by about 1.3-fold. Luteal cells obtained from ovaries 4 days after ovulation were much more responsive to LH than identically treated cells obtained 11 days after ovulation. Amplification of luteal cell responses to LH by adenosine also showed a marked inverse relationship with cell age. Prostaglandin F_2α (PGF_2α) inhibited LH-stimulated cAMP accumulation and progesterone secretion, but had little effect in the absence of LH. The half-maximal concentration for inhibition by PGF_2α of LH-stimulated cAMP accumulation was about 5 nM; maximum inhibition by PGF_2α (10 nM) was about 50%. PGF_2α had no effect on the ED₅₀ of LH for the stimulation of cAMP accumulation. Stimulation of progesterone secretion in response to low doses of LH (20 ng/ml) was completely inhibited by PGF_2α. At higher doses of LH, the inhibitory effect of PGF_2α on progesterone secretion was attenuated such that the ED₅₀ for LH was increased about 10-fold, with relatively little change in the maximum response. Adenosine attenuated the inhibitory effect of PGF_2α on LH-stimulated cAMP accumulation and progesterone secretion. For example, 50 μM adenosine increased the dose of PGF_2α required to produce maximal inhibition of LH-stimulated cAMP accumulation and progesterone secretion by about 100-fold. Higher levels of adenosine (100 μM) completely reversed the inhibitory effect of PGF_2α. Adenosine and PGF_2α were found to be competitive antagonists of LH-stimulated cAMP accumulation, and the inhibition constant of PGF_2α was 15 nM. Adenosine had no effect on receptorbinding activity of PGF_2α in luteal membranes, luteal cell uptake of PGF_2α, or PGF_2α production by luteal cells. Based on the present data and the ubiquitous nature of these substances in tissues, it is suggested that adenosine and PGF_2α may be regulators of luteal cell function by acute and local control of the expression of action of LH. (Endocrinology 110: 38, 1982).