Tumor necrosis factor alpha inhibits gonadotropin hormonal action in nontransformed ovarian granulosa cells. A modulatory noncytotoxic property
It has been suggested that resident ovarian macrophages may play a role in the regulation of ovarian function through local paracrine secretion of regulatory molecule(s). It is the objective of the in vitro studies reported herein to evaluate the potential ovarian relevance of one such macrophage pr...
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Published in | The Journal of biological chemistry Vol. 264; no. 20; pp. 11591 - 11597 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda, MD
American Society for Biochemistry and Molecular Biology
15.07.1989
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Subjects | |
Online Access | Get full text |
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Summary: | It has been suggested that resident ovarian macrophages may play a role in the regulation of ovarian function through local
paracrine secretion of regulatory molecule(s). It is the objective of the in vitro studies reported herein to evaluate the
potential ovarian relevance of one such macrophage product, tumor necrosis factor alpha (TNF-alpha). To this end, use was
made of a primary culture system of rat ovarian granulosa cells, the functional status of which was monitored by the acquisition
of estrogen, progestin, and proteoglycan biosynthetic capacity. Whereas treatment with the gonadotropin follicle-stimulating
hormone (FSH), a potent functional regulator, resulted in a substantial increase in the extent of aromatization (conversion
of androgenic steroid precursors to estrogens), concomitant exposure to TNF-alpha (10 ng/ml) produced significant (p less
than 0.05), yet reversible inhibition (71 +/- 7%) of this FSH effect. This specific activity of TNF-alpha was characterized
by a projected minimal effective dose of less than 0.1 ng/ml, an apparent median inhibitory dose of 0.56 +/- 0.14 ng/ml, and
a minimal time requirement of 48 h. Significantly, the direct effect of TNF-alpha could not be accounted for by a decrease
in cellular viability or plating efficiency, nor by a decrease in the number of cells or their DNA content. Instead, TNF-alpha
inhibited FSH hormonal action at the level of stimulatable adenylate cyclase activity, exerting no apparent effect either
at the level of the FSH receptor or at site(s) of action distal to cAMP generation. The effect of TNF-alpha was not limited
to the attenuation of estrogen biosynthesis, exerting qualitatively similar effects on FSH-supported progestin and proteoglycan
biosynthetic capacity. As such, these findings are in keeping with the notion that subnanomolar concentrations of TNF-alpha,
possibly of ovarian macrophage origin, may comprise the signal of a paracrine loop designed to attenuate gonadotropin action
thereby playing a potential role in the development and/or demise of the ovarian follicle. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |