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

Harold R. Behrman, Alan K. Hall, Sandra L. Preston, Steven D. Gore

Research output: Contribution to journalArticlepeer-review

Abstract

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 (PGF) 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 of LH-stimulated cAMP accumulation was about 5 nM; maximum inhibition by PGF (10 nM) was about 50%. PGF 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. At higher doses of LH, the inhibitory effect of PGF 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 on LH-stimulated cAMP accumulation and progesterone secretion. For example, 50 μM adenosine increased the dose of PGF 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. Adenosine and PGF were found to be competitive antagonists of LH-stimulated cAMP accumulation, and the inhibition constant of PGF was 15 nM. Adenosine had no effect on receptorbinding activity of PGF in luteal membranes, luteal cell uptake of PGF, or PGF 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 may be regulators of luteal cell function by acute and local control of the expression of action of LH. (Endocrinology 110: 38, 1982).

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalEndocrinology
Volume110
Issue number1
DOIs
StatePublished - Jan 1982

ASJC Scopus subject areas

  • Endocrinology

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