Cytokine-mediated regulation of ovarian function: tumor necrosis factor alpha inhibits gonadotropin-supported progesterone accumulation by differentiating and luteinized murine granulosa cells.
Current views favor the notion that resident ovarian macrophages play an in situ role in the regulation of ovarian function through the local secretion of regulatory molecule(s) (i.e., cytokines). Herein we report on the potential ovarian relevance of one such macrophage product, tumor necrosis factor (TNF) alpha, a polypeptide capable of oncolytic as well as pleiotropic noncytotoxic biologic activities. Our findings suggest that the ability of TNF alpha to diminish the gonadotropin-supported accumulation of progesterone by granulosa/luteal cells is largely due to attenuation of key biosynthetic steps leading to progesterone production. These findings are in keeping with the notion that TNF alpha, possibly of intraovarian (e.g., macrophage or granulosa cell) origin, may comprise the centerpiece of a regulatory loop designed to attenuate gonadotropin hormonal action. Acting at or adjacent to its site of synthesis, TNF alpha may thus partake in the modulation of ovarian progestin economy, possibly in connection with the death of the corpus luteum.
Adashi
E Y
EY
Department of Obstetrics and Gynecology, University of Maryland School of Medicine, Baltimore 21201.
Resnick
C E
CE
Packman
J N
JN
Hurwitz
A
A
Payne
D W
DW
D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis / Q000494:pharmacology; D016207:Cytokines; D005260:Female; D006062:Gonadotropins / Q000502:physiology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051379:Mice; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D011372:Progestins / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001685:Biological Factors; D003470:Culture Media; D016207:Cytokines; D006062:Gonadotropins; D011372:Progestins; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone