The mechanisms by which phorbol ester inhibits LH stimulation of progesterone production in rat granulosa cells.

Abstract:

:Tumor-promoting phorbol esters are believed to affect cell functions by activating a Ca+2-and lipid-dependent protein kinase (protein kinase C). 12-0-Tetradecanoyl phorbol-13-acetate (TPA) inhibits LH stimulation of progesterone (P) accumulation in rat granulosa cells. To determine the mechanisms by which TPA inhibits LH stimulation of P accumulation, TPA regulation of various ovarian steroidogenic enzymes was investigated. Cells were obtained from immature (28-29 days old) rats 48 h after injection of 20 IU PMSG and incubated for up to 5 h. TPA decreased the P responses to LH, cholera toxin, and (Bu)2cAMP by 20%, 24%, and 28%, respectively. One locus of inhibition of LH action, therefore, was after cAMP. TPA decreased LH-stimulated 3-beta-hydroxysteroid dehydrogenase activity. Furthermore, TPA stimulated 20-alpha-hydroxysteroid dehydrogenase activity. The combination of TPA and A23187 inhibited LH-stimulated P accumulation to the same extent as TPA alone. These data suggest that TPA-induced decreases in LH-stimulated P production result from both the inhibition of P biosynthesis and the stimulation of P breakdown.

journal_name

Endocr Res

journal_title

Endocrine research

authors

Kawai Y,Clark MR

doi

10.1080/07435808609035438

subject

Has Abstract

pub_date

1986-01-01 00:00:00

pages

211-28

issue

3

eissn

0743-5800

issn

1532-4206

journal_volume

12

pub_type

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