Arachidonic acid inhibits luteinizing hormone-stimulated progesterone production in hen granulosa cells

Alan Leslie Johnson, J. L. Tilly

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Arachidonic acid has been proposed to function as a hormone-induced second messenger in a variety of mammalian endocrine tissues. The present studies were conducted to evaluate whether arachidonic acid, either added exogenously or released endogenously following treatment with physiologic (phospholipase A2) or pharmacologic (melittin) agents, influences basal and/or luteinizing hormone (LH)-induced cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in granulosa cells from domestic hens. Phospholipase A2 (PLA2) and melittin treatments failed to alter basal concentrations of progesterone, whereas arachidonic acid had a slight stimulatory effect (only at the 50-μM dose) on progesterone levels, and no effect on cAMP. By contrast, arachidonic acid, PLA2, and melittin each inhibited LH-promoted progesterone production in a dose-dependent fashion. The inhibitory effects of arachidonic acid on the progesterone response were determined to occur both prior and subsequent to cAMP formation since cAMP levels in arachidonic acid-treated cells were attenuated after treatment with 10 ng LH or 100 μM forskolin (at 10- to 100-μM doses of arachidonic acid), and progesterone production was decreased in the presence of 1 mM 8-bromo-cAMP (with 50 and 100 μM arachidonic acid). The post-cAMP mechanism of action is characterized by the inability of cells to convert 25-hydroxycholesterol, but not pregnenolone, to progesterone. The effects of arachidonic acid are probably direct, since pharmacologic inhibitors of the lipoxygenase (nordihydroguaiaretic acid) and cyclooxygenase (indomethacin) pathways of arachidonic acid metabolism failed to alter the suppression of LH-stimulated progesterone production. Furthermore, several related fatty acids (pentaenoic, eicosatrienoic, oleic, and palmitoleic acids), which do not enter the cyclooxygenase or lipoxygenase metabolic pathway, replicated this response. We conclude that arachidonic acid may represent an additional second messenger that can modulate LH-stimulated steroidogenesis in the ovary of the hen.

Original languageEnglish (US)
Pages (from-to)458-464
Number of pages7
JournalBiology of reproduction
Volume42
Issue number3
DOIs
StatePublished - Jan 1 1990

Fingerprint

Granulosa Cells
Luteinizing Hormone
Arachidonic Acid
Progesterone
Cyclic AMP
Melitten
Phospholipases A2
Second Messenger Systems
Prostaglandin-Endoperoxide Synthases
Masoprocol
Oleic Acids
Lipoxygenase Inhibitors
Pregnenolone
Lipoxygenase
Colforsin
Metabolic Networks and Pathways
Indomethacin
Ovary
Fatty Acids
Hormones

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

@article{bdedbd3e283f43c389eefaf1ad1f1c5a,
title = "Arachidonic acid inhibits luteinizing hormone-stimulated progesterone production in hen granulosa cells",
abstract = "Arachidonic acid has been proposed to function as a hormone-induced second messenger in a variety of mammalian endocrine tissues. The present studies were conducted to evaluate whether arachidonic acid, either added exogenously or released endogenously following treatment with physiologic (phospholipase A2) or pharmacologic (melittin) agents, influences basal and/or luteinizing hormone (LH)-induced cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in granulosa cells from domestic hens. Phospholipase A2 (PLA2) and melittin treatments failed to alter basal concentrations of progesterone, whereas arachidonic acid had a slight stimulatory effect (only at the 50-μM dose) on progesterone levels, and no effect on cAMP. By contrast, arachidonic acid, PLA2, and melittin each inhibited LH-promoted progesterone production in a dose-dependent fashion. The inhibitory effects of arachidonic acid on the progesterone response were determined to occur both prior and subsequent to cAMP formation since cAMP levels in arachidonic acid-treated cells were attenuated after treatment with 10 ng LH or 100 μM forskolin (at 10- to 100-μM doses of arachidonic acid), and progesterone production was decreased in the presence of 1 mM 8-bromo-cAMP (with 50 and 100 μM arachidonic acid). The post-cAMP mechanism of action is characterized by the inability of cells to convert 25-hydroxycholesterol, but not pregnenolone, to progesterone. The effects of arachidonic acid are probably direct, since pharmacologic inhibitors of the lipoxygenase (nordihydroguaiaretic acid) and cyclooxygenase (indomethacin) pathways of arachidonic acid metabolism failed to alter the suppression of LH-stimulated progesterone production. Furthermore, several related fatty acids (pentaenoic, eicosatrienoic, oleic, and palmitoleic acids), which do not enter the cyclooxygenase or lipoxygenase metabolic pathway, replicated this response. We conclude that arachidonic acid may represent an additional second messenger that can modulate LH-stimulated steroidogenesis in the ovary of the hen.",
author = "Johnson, {Alan Leslie} and Tilly, {J. L.}",
year = "1990",
month = "1",
day = "1",
doi = "10.1095/biolreprod42.3.458",
language = "English (US)",
volume = "42",
pages = "458--464",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "3",

}

Arachidonic acid inhibits luteinizing hormone-stimulated progesterone production in hen granulosa cells. / Johnson, Alan Leslie; Tilly, J. L.

In: Biology of reproduction, Vol. 42, No. 3, 01.01.1990, p. 458-464.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Arachidonic acid inhibits luteinizing hormone-stimulated progesterone production in hen granulosa cells

AU - Johnson, Alan Leslie

AU - Tilly, J. L.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - Arachidonic acid has been proposed to function as a hormone-induced second messenger in a variety of mammalian endocrine tissues. The present studies were conducted to evaluate whether arachidonic acid, either added exogenously or released endogenously following treatment with physiologic (phospholipase A2) or pharmacologic (melittin) agents, influences basal and/or luteinizing hormone (LH)-induced cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in granulosa cells from domestic hens. Phospholipase A2 (PLA2) and melittin treatments failed to alter basal concentrations of progesterone, whereas arachidonic acid had a slight stimulatory effect (only at the 50-μM dose) on progesterone levels, and no effect on cAMP. By contrast, arachidonic acid, PLA2, and melittin each inhibited LH-promoted progesterone production in a dose-dependent fashion. The inhibitory effects of arachidonic acid on the progesterone response were determined to occur both prior and subsequent to cAMP formation since cAMP levels in arachidonic acid-treated cells were attenuated after treatment with 10 ng LH or 100 μM forskolin (at 10- to 100-μM doses of arachidonic acid), and progesterone production was decreased in the presence of 1 mM 8-bromo-cAMP (with 50 and 100 μM arachidonic acid). The post-cAMP mechanism of action is characterized by the inability of cells to convert 25-hydroxycholesterol, but not pregnenolone, to progesterone. The effects of arachidonic acid are probably direct, since pharmacologic inhibitors of the lipoxygenase (nordihydroguaiaretic acid) and cyclooxygenase (indomethacin) pathways of arachidonic acid metabolism failed to alter the suppression of LH-stimulated progesterone production. Furthermore, several related fatty acids (pentaenoic, eicosatrienoic, oleic, and palmitoleic acids), which do not enter the cyclooxygenase or lipoxygenase metabolic pathway, replicated this response. We conclude that arachidonic acid may represent an additional second messenger that can modulate LH-stimulated steroidogenesis in the ovary of the hen.

AB - Arachidonic acid has been proposed to function as a hormone-induced second messenger in a variety of mammalian endocrine tissues. The present studies were conducted to evaluate whether arachidonic acid, either added exogenously or released endogenously following treatment with physiologic (phospholipase A2) or pharmacologic (melittin) agents, influences basal and/or luteinizing hormone (LH)-induced cyclic adenosine 3',5'-monophosphate (cAMP) and progesterone production in granulosa cells from domestic hens. Phospholipase A2 (PLA2) and melittin treatments failed to alter basal concentrations of progesterone, whereas arachidonic acid had a slight stimulatory effect (only at the 50-μM dose) on progesterone levels, and no effect on cAMP. By contrast, arachidonic acid, PLA2, and melittin each inhibited LH-promoted progesterone production in a dose-dependent fashion. The inhibitory effects of arachidonic acid on the progesterone response were determined to occur both prior and subsequent to cAMP formation since cAMP levels in arachidonic acid-treated cells were attenuated after treatment with 10 ng LH or 100 μM forskolin (at 10- to 100-μM doses of arachidonic acid), and progesterone production was decreased in the presence of 1 mM 8-bromo-cAMP (with 50 and 100 μM arachidonic acid). The post-cAMP mechanism of action is characterized by the inability of cells to convert 25-hydroxycholesterol, but not pregnenolone, to progesterone. The effects of arachidonic acid are probably direct, since pharmacologic inhibitors of the lipoxygenase (nordihydroguaiaretic acid) and cyclooxygenase (indomethacin) pathways of arachidonic acid metabolism failed to alter the suppression of LH-stimulated progesterone production. Furthermore, several related fatty acids (pentaenoic, eicosatrienoic, oleic, and palmitoleic acids), which do not enter the cyclooxygenase or lipoxygenase metabolic pathway, replicated this response. We conclude that arachidonic acid may represent an additional second messenger that can modulate LH-stimulated steroidogenesis in the ovary of the hen.

UR - http://www.scopus.com/inward/record.url?scp=0025265218&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025265218&partnerID=8YFLogxK

U2 - 10.1095/biolreprod42.3.458

DO - 10.1095/biolreprod42.3.458

M3 - Article

C2 - 2111185

AN - SCOPUS:0025265218

VL - 42

SP - 458

EP - 464

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 3

ER -